重组基因工程抗体和蛇毒C型凝集素类似蛋白在毕赤酵母中表达及结构功能研究
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摘要
巴斯德毕赤甲醇营养型酵母(Pichia Pastoris)属于低等的真核表达系统，与其他表达系统相比，具有遗传操作简单、蛋白折叠和二硫键加工能力较强、易于高密度发酵、蛋白表达量较高等优点，已经成为重组蛋白研究和商业化生产的重要表达系统之一。本论文讨论了抗ErbB2基因工程抗体和重组蛇毒毒素蛋白在毕赤酵母中表达，以及结构和功能关系研究中，主要包括以下三部分内容：
1．密码子优化的抗ErbB2单链抗体在Pichia中表达、纯化和活性鉴定。ErbB2／HER2／P185属于具有酪氨酸激酶的表皮生长因子受体家族，在细胞生长发育和组织分化中起到了重要作用，ErbB2过表达经常在细胞癌化和肿瘤发生中起关键的作用，因此成为肿瘤诊断和治疗的一个重要靶分子。本实验室研制了一株具有肿瘤生长抑制活性的抗ErbB2单克隆抗体mA21，并且构建和表达了工程化的单链嵌和抗体chA21。本研究就是在前期工作基础上合成了密码子优化的单链抗体scFv全基因，并且在Pichia酵母中获得了高效表达，进一步优化表达条件后单链抗体表达量达到了10mg/L。单链抗体经Ni2+亲和柱一步纯化后，即可用于晶体生长、亲和力测定等结构和功能研究。
2．抗ErbB2胞外区抗体A21的表位鉴定、晶体结构分析和抗肿瘤机理的初步研究。我们联合使用噬菌体随机肽库表面展示技术、抗原在原核系统中分段表达、抗原点突变扫描等实验精细测定了A21抗体识别的抗原表位和关键性残基。在蛋白质结构晶体实验室的帮组下解析了A21单链抗体2.1A分辨率的晶体结构。并且利用大分子对接软件，基于实验结果预测并验证了A21抗体与ErbB2抗原可能的相互作用模型。结果显示A21抗体主要识别ErbB2胞外区靠近N端I区的空间表位。我们还测定了A21抗体对肿瘤细胞株的增殖抑制活性、抗体的内吞作用、抗体对ErbB2磷酸化的影响、以及抗体诱导的ErbB2受体下调作用，进一步解释了A21抗体表位和抗体功能之间的联系。
3．重组蛇毒C型凝集素类似蛋白ACFI在Pichia酵母中表达、纯化和结构功能关系研究。蛇毒C型凝集素类似蛋白具有非常相似的二硫键连接的异二聚体结构，但是具有多种不同的生物学功能。ACFI是从皖南尖吻蝮蛇蛇毒中分离到的一种可以与凝血因子结合的具有抗凝活性的C型凝集素类似蛋白。我们设计了一种新的共转化策略，使用两个不同抗生素选择标记的载体用于筛选ACFI两个亚基共表达的重组菌株。结果显示，重组ACFI亚基在Pichia酵母中单独表达时形成同二聚体，共表达时则可以形成异二聚体。重组ACFI具有与天然蛋白类似的凝血因子结合活性和抗凝活性，但是重组亚基却没有这些功能，说明ACFI两个亚基对维持其正常的生物学功能具有非常重要和不可替代的作用。我们的结果提示Pichia系统在蛇毒C型凝集素类似蛋白结构和功能关系的研究中具有重要的应用价值。
The methylotrophic yeast Pichia Pastoris is a single-cell microorganism as well as a eukaryote. The P. pastoris expression system combines some of the advantages of both the bacterial and eucaryotic systems, e.g. efficient in disulfide-bond folding and post-transcriptional processing, and also easy for manipulation, culture and fermentation, thus it has been widely used for high-level expression of thousands of heterologous proteins for both basic laboratory research and industrial manufacture. In my dissertation, we showed the application of P. pastoris in expressing engineered antibody fragments and recombinant snake toxins for structure-function study, mainly including three chapters:
1. Codon optimization, expression, purification and characterization of the anti-ErbB2 single-chain antibody (scFv). ErbB2/HER2/P185 belongs to the epidermal growth factor receptor (EGFR) family, and as a tyrosine kinase receptor it plays an important role in regulating normal cell growth and differentiation. ErbB2-overexpression is often associated with cell transformation and tumorigenesis, making it an attractive target in tumor diagnoses and therapy. In the previous study, we generated a monoclonal antibody mA21 against ErbB2 extracellular domain, and the engineered single-chain chimeric antibody chA21 also exhibited potentials in inhibition of ErbB2-overexpressing tumor cells. We synthesized the condo-optimal full-length scFv gene and expressed it in P. pastoris. After further optimization of culture and induction conditions, the scFv expression level was achieved to 10mg/L. The secreted scFv was purified by one-step Ni2+ chelating chromatography and then used for biological function studies.
2. Epitope mapping, crystal structure analysis and functional mechanism study of the A21 anti-ErbB2 antibodies. We precisely located the A21 epitope site and determined possible contacing residues by combinatorial utilization of phage peptide library screening, GST-fusion domain expression and mutagenesis scanning in E.coli. We then determined the 2.1 A crystal structure of the scFv expressed in P. pastoris and proposed the A21 scFv-ErbB2 complex model by molecular docking. These results suggested that A21 recognizes a conformational epitope mainly compassing ErbB2 subdomain I. We also determined the internalization ability of A21 antibodies as well as their effects on tumor cell growth, ErbB2 phosphorylation and down-regulation. Based on these findings we further discussed the relationship between the epitopes of anti-ErbB2 antibodies and functional mechanisms.
3. Expression, purification and functional study of a recombinant C-type lectin-like protein (CLP) ACFI in P. pastoris. Snake CLPs have similar structures consisting of two disulfide-linked subunits but diverse functions. ACFI is an anticoagulant CLP isolated from Agkistrodon acutus venom, which could bind to coagulation factors IX and X. We expressed the two subunits of ACFI in P. pastoris by a novel co-transforming strategy using two vectors with different selectable markers. Recombinant homodimers were secreted when the ACFI subunits were expressed alone, while heterodimers (rACFI) secreted when two subunits co-expressed. rACFI retained both the coagulation factors-binding activity and APTT-prolonging activity similar to nature ACFI, but recombinant homodimers completely lost these activities, indicating the heterodimerization of two subunits is required for its function. It also suggests that P. pastoris is a promising system for structure-function studies of snake CLPs.
1．密码子优化的抗ErbB2单链抗体在Pichia中表达、纯化和活性鉴定。ErbB2／HER2／P185属于具有酪氨酸激酶的表皮生长因子受体家族，在细胞生长发育和组织分化中起到了重要作用，ErbB2过表达经常在细胞癌化和肿瘤发生中起关键的作用，因此成为肿瘤诊断和治疗的一个重要靶分子。本实验室研制了一株具有肿瘤生长抑制活性的抗ErbB2单克隆抗体mA21，并且构建和表达了工程化的单链嵌和抗体chA21。本研究就是在前期工作基础上合成了密码子优化的单链抗体scFv全基因，并且在Pichia酵母中获得了高效表达，进一步优化表达条件后单链抗体表达量达到了10mg/L。单链抗体经Ni2+亲和柱一步纯化后，即可用于晶体生长、亲和力测定等结构和功能研究。
2．抗ErbB2胞外区抗体A21的表位鉴定、晶体结构分析和抗肿瘤机理的初步研究。我们联合使用噬菌体随机肽库表面展示技术、抗原在原核系统中分段表达、抗原点突变扫描等实验精细测定了A21抗体识别的抗原表位和关键性残基。在蛋白质结构晶体实验室的帮组下解析了A21单链抗体2.1A分辨率的晶体结构。并且利用大分子对接软件，基于实验结果预测并验证了A21抗体与ErbB2抗原可能的相互作用模型。结果显示A21抗体主要识别ErbB2胞外区靠近N端I区的空间表位。我们还测定了A21抗体对肿瘤细胞株的增殖抑制活性、抗体的内吞作用、抗体对ErbB2磷酸化的影响、以及抗体诱导的ErbB2受体下调作用，进一步解释了A21抗体表位和抗体功能之间的联系。
3．重组蛇毒C型凝集素类似蛋白ACFI在Pichia酵母中表达、纯化和结构功能关系研究。蛇毒C型凝集素类似蛋白具有非常相似的二硫键连接的异二聚体结构，但是具有多种不同的生物学功能。ACFI是从皖南尖吻蝮蛇蛇毒中分离到的一种可以与凝血因子结合的具有抗凝活性的C型凝集素类似蛋白。我们设计了一种新的共转化策略，使用两个不同抗生素选择标记的载体用于筛选ACFI两个亚基共表达的重组菌株。结果显示，重组ACFI亚基在Pichia酵母中单独表达时形成同二聚体，共表达时则可以形成异二聚体。重组ACFI具有与天然蛋白类似的凝血因子结合活性和抗凝活性，但是重组亚基却没有这些功能，说明ACFI两个亚基对维持其正常的生物学功能具有非常重要和不可替代的作用。我们的结果提示Pichia系统在蛇毒C型凝集素类似蛋白结构和功能关系的研究中具有重要的应用价值。
The methylotrophic yeast Pichia Pastoris is a single-cell microorganism as well as a eukaryote. The P. pastoris expression system combines some of the advantages of both the bacterial and eucaryotic systems, e.g. efficient in disulfide-bond folding and post-transcriptional processing, and also easy for manipulation, culture and fermentation, thus it has been widely used for high-level expression of thousands of heterologous proteins for both basic laboratory research and industrial manufacture. In my dissertation, we showed the application of P. pastoris in expressing engineered antibody fragments and recombinant snake toxins for structure-function study, mainly including three chapters:
1. Codon optimization, expression, purification and characterization of the anti-ErbB2 single-chain antibody (scFv). ErbB2/HER2/P185 belongs to the epidermal growth factor receptor (EGFR) family, and as a tyrosine kinase receptor it plays an important role in regulating normal cell growth and differentiation. ErbB2-overexpression is often associated with cell transformation and tumorigenesis, making it an attractive target in tumor diagnoses and therapy. In the previous study, we generated a monoclonal antibody mA21 against ErbB2 extracellular domain, and the engineered single-chain chimeric antibody chA21 also exhibited potentials in inhibition of ErbB2-overexpressing tumor cells. We synthesized the condo-optimal full-length scFv gene and expressed it in P. pastoris. After further optimization of culture and induction conditions, the scFv expression level was achieved to 10mg/L. The secreted scFv was purified by one-step Ni2+ chelating chromatography and then used for biological function studies.
2. Epitope mapping, crystal structure analysis and functional mechanism study of the A21 anti-ErbB2 antibodies. We precisely located the A21 epitope site and determined possible contacing residues by combinatorial utilization of phage peptide library screening, GST-fusion domain expression and mutagenesis scanning in E.coli. We then determined the 2.1 A crystal structure of the scFv expressed in P. pastoris and proposed the A21 scFv-ErbB2 complex model by molecular docking. These results suggested that A21 recognizes a conformational epitope mainly compassing ErbB2 subdomain I. We also determined the internalization ability of A21 antibodies as well as their effects on tumor cell growth, ErbB2 phosphorylation and down-regulation. Based on these findings we further discussed the relationship between the epitopes of anti-ErbB2 antibodies and functional mechanisms.
3. Expression, purification and functional study of a recombinant C-type lectin-like protein (CLP) ACFI in P. pastoris. Snake CLPs have similar structures consisting of two disulfide-linked subunits but diverse functions. ACFI is an anticoagulant CLP isolated from Agkistrodon acutus venom, which could bind to coagulation factors IX and X. We expressed the two subunits of ACFI in P. pastoris by a novel co-transforming strategy using two vectors with different selectable markers. Recombinant homodimers were secreted when the ACFI subunits were expressed alone, while heterodimers (rACFI) secreted when two subunits co-expressed. rACFI retained both the coagulation factors-binding activity and APTT-prolonging activity similar to nature ACFI, but recombinant homodimers completely lost these activities, indicating the heterodimerization of two subunits is required for its function. It also suggests that P. pastoris is a promising system for structure-function studies of snake CLPs.
引文
Berezov 2002, A., Chen, J., Liu, Q., Zhang, H.T., Greene, M.I. and Murali.R. Disabling receptor ensembles with rationally designed interface peptidomimetics. J. Biol. Chem. 2005, 277: 28330-28339.
Borg JP, Marchetto S, Le Bivic A, Ollendorff V, Jaulin-Bastard F, Saito H, Foumier F, Adelaide J, Margolis B, Birnbaum D. ERBIN: abasolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor. Nat Cell Biol 2002: 407-414.
Burgess A. W., Cho H. S., Eigenbrot, K., Ferguson, K.M., Thomas P.J. Garrett, Leahy D.J., Lemmon, M. A.,Siiwkowski, M.X, Ward, C.W, Yokoyama, S. An open-and-shut case? Review recent insights into the activation of EGF/ErbB receptors. Mol. Cell. 2003, 12: 541-552.
Camenisch T.D., Schroeder J.A, Bradley J., Klewer S.E., Mcdonald J.A. Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2-ErbB3 receptors. Nat. Medicine 2002, 8: 850-855.
Cho H.S., Mason K., Ramyar K.X., Stanley A.M., Gabelli S.B., Denney D.W., Leahy D.J. (2003) Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421: 756-760.
Claesson-Welsh L. Signal transduction by receptor tyrosine kinases. Toxicol. Vitro. 1998, 12: 525-536.
Coussens L., Yang-Feng T.L., Liao Y.C., Chen E., Gray A., McGrath J., Seeburg P.H., Libermann T.A., Schlessinger J., Francke U., Levinson A., Ullrich A. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 1985,230: 1132-1139.
Franklin M.C., Carey K.D., Vajdos F.F., Leahy D.J, Vos A.M, Sliwkowski M.X. Insights into ErbB2 signaling from the structure of the ErbB2-pertusumab complex. Cancer Cell 2004,5: 317-327.
Garratt A.N., Ozcelik C, Birchmeier C. ErbB2 Pathways in Heart and Neural Diseases. Trends Cardiovasc. Med. 2003,13: 80-86.
Graus-Porta D., Beerli R.R., Daly J.M., Hynes N.E. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. The EMBO J. 1997,16:1647-1655.
Hommelgaard A.M., Lerdrup M., Van Deurs B. Association with membrane protrusions makes ErbB2 an intemalization-resistant receptor. Mol Biol Cell 2004, 15: 1557-67.
Hynes N.E., Horsch K., Olayioye M.A., Badache A. The ErbB receptor tyrosine family as signal integrators. Endocrine-Related Cancer 2001, 8: 151-159.
Jaulin-Bastard F, Saito H, Le Bivic A, Ollendorff V, Marchetto S, Birnbaum D, Borg JP. The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins. J Biol. Chem. 2001, 276: 15256-15263.
Lidke D.S., Nagy P., Heintamann R., Arndt-Jovin D., Post J.N., Grecco H.E., Jares-Erijman E.A., Jovin T.M. Quantum dot ligands provide new insights into erbB/Her receptor-mediated signal transduction. Nat. Biotechnol. 2004, 22: 198-203.
Marmor M.D., Skaria K.B., M. Sc, Yarden Y. Signal Transduction And Oncogenesis By Erbb/Her Receptors. Int. J. Radiation Oncol. 2004, 58: 903-913.
Nancy E.H., Heidi A., Lane N. Erbb receptors and cancer: the complexity of targeted inhibitors Nat. Rev. Cancer 2005,5: 341-354.
Olayioye M.A., Neve R.M., Lane H.A., Hynes N.A. The ErbB signaling network: receptor heterodimerization in development and cancer, The EMBO J. 2000,19: 3159-3167.
Olayioye M.A., Neve R.M., Lane, H.A. Hynes H.E. The ErbB signaling network: receptor heterodimerization in development and cancer. The EMBO J. 2000,19: 3159-3167.
Richard C, William R. H., Michael A. L., Sarah E.H., William J.M. The Catalytic Activity of the ErbB-2 Receptor Tyrosine Kinase Is Essential for Embryonic Development. Molecular and Cellular Biology 2002, Feb: 1073-1078.
Robert R..J. The ErbB/HER receptor protein-tyrosine kinases and cancer. BBRC 2004, 319:1-11. Saxon M.L., Lee D.C. Mutagenesis reveals a role for epidermal growth factor receptor extracellular subdomain IV in ligand binding. J. Biol. Chem. 1999,274: 28356-28362.
Schneider J.W., Chang A.Y., Rocco T.P. Cardiotoxicity in signal transduction therapeutics: erbB2 antibodies and the heart. Semin. Oncol. 2001,28: S18-S26.
Semba K, Kamata N, Toyoshima K, Yamamoto T. A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erb-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc. Natl. Acad. Sci. 1985, 82: 6497-6501.
Shelly M, Mosesson Y, Citri A, Lavi S, Zwang Y, Melamed-Book N, Aroeti B, Yarden Y. Polar expression of
ErbB-2/HER2 in epithelia, Bimodal regulation by Lin-7. Dev. Cell 2003, 5: 475-486.
Shih C, Padhy L.C., Murray M., Weinberg R.A. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature 1981,290:261-264.
Uray I.P, Connelly J.H., Thoma'zy V, Shipley G.L., Vaughn V.K., Frazier H., Taegtmeyer H., Davies J.A. Left Ventricular Unloading Alters Receptor Tyrosine Kinase Expression in the Failing Human Heart. J. Heart Lung Transplant. 2002 July: 771-782.
Waterman H., Yarden Y. Molecular mechanisms underlying endocytosis and sorting of ErbB Wiley H.S.Trafficking of the ErbB receptors and its influence on signaling. Experimental Cell Research 2003, 284: 78-88.
Yarden Y. Biology of HER2 and its importance in breast cancer. Oncology 2001, 61: S1-S13.
Yarden Y., Sliwkowski M.X. Untangling the ErbB2 signaling network, Nat. Rev. Mol. Cell Biol. 2001b, 2: 127-136.
Hynes NE, Stem DF. The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim Biophys Acta. 1994, 1198:165-84
Ross J.S., Fletcher J.A. The HER2/neu oncogene: prognostic factor, predictive factor and target for therapy. Semin. Cancer Biol. 1999, 9: 125-138.
Piccart M, Lohrisch C., Leo A.D., Larsimont D. The Predictive Value of HER2 in Breast Cancer. Oncology 2001, 61: S73-S82.
Neve R. M., Lane H.A., Hynes N. E. The role of overexpressed HER2 in transformation. Annals of Oncology 2001, 12: S9-S13.
Pinkas-Kramarski R, Shelly M, Guarino BC, WangLM, Lyass L, Alroy I, Alimandi M, Kuo A, Moyer JD, Lavi S,
Eisenstein M, Ratzkin BJ, Seger R, Bacus SS, Pierce JH, Andrews GC, Yarden Y, Alamandi M: ErbB tyrosine kinases and the two neuregulin families constitute a ligand-receptor network. Mol. Cell Biol. 1998, 18:6090-6101.
Holbro T., Beerli R.R., Maurer F., Koziczak M., Barbas C.F., Hynes N. E. The ErbB2-ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. PNAS 2003, 100: 8933-8938.
Hsieh S.S., Malerczyk C., Aigner A., Czubayko F. ErbB-2 expression is rate-limiting for epidermal growth factor-mediated stimulation of ovarian cancer cell proliferation. Int. J. Cancer 2000, 86:644-651.
Neve, R. M., Lane, H.A., Hynes, N.E. The role of overexpressed HER2 in transformation, Annals of Oncology 2001, 12: S9-S13.
Timms JF, White SL, O'Hare M J, Waterfield MD. Effects of ErbB-2 overexpression on mitogenic signalling and cell cycle progression in human breast luminal epithelial cells, Oncogene. 2002, 21: 6573-6586.
Muraoka R. S, Anne E., Lenferink G., Law B., Hamilton E., Brantley D.M., Roebuck L.R, Arteaga C.L. ErbB2/Neu-Indueed, cyclin D1-dependent transformation is accelerated in p27-haploinsufficient mammary epithelial cells but impaired in p27-nuli cells. Mol. Cell. Biol. 2002, 22:2204-2219.
Jones S.M, Kazlauskas A., Growth factor-dependent signaling and cell cycle progression. FEBS Letters 2001, 490:110-116.
Zhou B. P., Liao Y, Xia W, Spohn B, Lee MH, Hung MC. Cytoplsmic localization of p21~(cip1/WAF1) by Akt-induced phosphorylation in HER2/neu-overexpressiong cells. Nat. Cell Biol. 2001, 3: 245-252.
Zhou B.P., Hu M.C., Miller S.A., Yu Z., Xia W., Lin S.Y., Hung M.C. Her-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway. J. Biol. Chem. 2000, 275:8027-8031.
Yang C., Ionescu-Tiba V., Bums K., Gadd M., Zukerberg L., Louis D.N., Sgroi D., Schmidt E.V. The role of the cyclin D1-dependent kinases in ErbB2-mediated breast cancer. Am. J. Pathol. 2004, 164:1031-1038.
Grossman S.R. p300/MDM2 complexs participate in MDM2-mediated p53 degradation. Mol. Cell 1998, 2: 405-415.
Tan M., Jing T., Lan K.H., Neal C.L. Phosphoraylation on Tyrosine-15 of p34Cdc2 by ErbB2 inhibits p34Cdc2activation and is involved in resistence to taxol-induced apoptosis. Mol. Cell 2002, 9: 993-1004.
Codony-Servat J., Albanell J., Lopez-Talavera J.C. et al. Cleavage of the HER2 ectodomain is a pervanadate-activable process that is inhibited by the tissue inhibitor of metalloproteases-1 in breast cancer cells. Cancer Res. 1999, 59: 1196-1201.
Huang H.S., Nagane M., Klingbeil C.K. et al. The enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers is mediated by threshold levels of constitutive tyrosine phosphorylation and unattenuated signaling. J. Biol. Chem.1997,272: 2927-2935.
Christianson T.A., Doherty J.K., Lin Y.J. et al. NH2-terminally truncated HER-2/neu protein: Relationship with shedding of the extracellular domain and with prognostic factors in breast cancer. Cancer Res 1998, 58: 5123-5129.
Worthylake R., Opresko L.K., Wiley H.S. ErbB2 amplification inhibits down-regulation and induces constitutive activation of both ErbB2 and epidermal growth factor receptors, J. Biol. Chem. 1999, 274: 8865-8874.
Hendriks B.S., Opresko L.K, Wiley H.S., Lauffenburger D. Coregulation of Epidermal Growth Factor Receptor/Human Epidermal Growth Factor Receptor 2 (HER2) Levels and Locations: Quantitative Analysis of HER2 Overexpression Effects, Cancer Res. 2003,63: 1130-1137.
Hendriks B.S., Opresko L.K., Wiley H.S., Lauffenburger D. Quantitative analysis of HER2-mediated effects on HER2 and epidermal growth factor receptor endocytosis: distribution of homo- and heterodimers depends on relative HER2 levels. J Biol. Chem. 2003, 278: 23343-23351.
Muthuswamy S.K., Gilman M., Brugge J.S. Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers. Mol. Cell. Biol. 1999,19: 6845-6857.
Verbeeka B.S., Adriaansen-Slota S.S., Vroomb T.M., Beckersc T., Rijksena G. Overexpression of EGFR and c-erbB2 causes enhanced cell migration in human breast cancer cells and NIH3T3 fibroblasts. FEBS Letters 1998, 425: 145-150.
Feldner J.C., Brandt B.H. Cancer cell motility—on the road from c-erbB-2 receptor steered signaling to actin reorganization. Exp. Cell. Res. 2002, 272: 93-108.
Dittmar T., Husemann A., Schewe Y., Nofer J.R., Niggemann B., Zanker K.S., Brandt B.H. Induction of cancer cell migration by epidermal growth factor is initiated by specific phosphorylation of tyrosine 1248 of c-erbB-2 receptor via EGFR. FASEB J. 2002, 16: 1823-1825.
Kathryn S.R. Spencer, Diana Graus-Porta, Jie Leng, Nancy E. Hynes, Richard L. Klemke. ErbB2 is necessary for induction of carcinoma cell invasion by ErbB family receptor tyrosine kinases. The Journal of Cell Biology, 2000; 148: 385-397.
Shepherd T.G., Kockeritz L., Szrajber M.R., Muller W.J., Hassell J.A. The pea3 subfamily ets genes are required for HER2/Neumediated mammary oncogenesis. Current Biology 2001,11: 1739-1748.
Nagae Y., Kameyama K., Yokoyama M, Naito Z., Yamada N., Maeda S., Asano G., Sugisaki Y., Tanaka S.. Expression of E-cadherin catenin and C-erbB-2 gene products in invasive ductal-type breast carcinomas. J. Nippon. Med.Sch. 2002,69: 165-171.
Wobus M, Rangwala R, Sheyn I, Hennigan R, Coila B, Lower EE, Yassin RS, Sherman LS. CD44 associates with EGFR and erbB2 in metastasizing mammary carcinoma cells. Appl Immunohistochem Mol. Morphol. 2002, 10: 34-39.
Jepson S, Komatsu M, Haq B, Arango ME, Huang D, Carraway CA, Carraway KL. Muc4/ sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Oncogene 2002,21: 7524-7532.
Adams G.P., Schier R., McCall A.M., Simmons H.H., Horak E.M., Alpaugh R.K., Marks J.D., Weiner L.M. High Affinity Restricts the Localization and Tumor Penetration of Single-Chain Fv Antibody Molecules, Cancer Res. 2001, 61: 4750—4755.
Arteaga C.L., Winnier A.R., Poirier M.C., Lopex-Larraza D.M., Shawver L.K., Hurd S.D., Stewart S.J. P185 c-erbB-2 signal enhances cisplatin-induced cytotoxicity in human breast carcinoma cells: association between an oncogenic receptor tyrosine kinase and drug-induced DNA repair. Cancer Res 1994, 54: 3758-3763.
Austin C.D., De Maziere A.M., Pisacane P.I., Van Dijk S.M., Eigenbrot C., Sliwkowski M.X., Klumperman J., Scheller R.H. Endocytosis and Sorting of ErbB2 and the Site of Action of Cancer Therapeutics Trastuzumab and Geldanarnycin. Mol Biol Cell 2004,15: 5268-82.
Bacus S.S., Stancovski I, Huberman E, Chin D, Hurwitz E, Mills G B, Ullrich A, Sela M, Yarden Y Tumor-inhibitory monoclonal antibodies to the HER-2/Neu receptor induce differentiation of human breast cancer cells. Cancer Res 1992, 52:2580.
Baselga J., Albanell J. (2001) Mechanism of action of anti-HER2 monoclonal antibodies. Ann. Oncol. S1:35-41.
Becerril B., Poul M.A., Marks J.D. Toward Selection of Internalizing Antibodies from Phage Libraries. Biochem. Biophys. Res. Commun. 1999, 255: 386-393.
Boyer C.M., Pusztai L., Wiener J.R., Xu F.J., Dean G.S, Bast B.S., O'Briant K.C., Greenwald M., Desombere K.A., Bast R.C. Relative cytotoxic activity of immunotoxins reactive with different epitopes on the extracellular domain of the c-erbb-2 (her-2/neu) gene product pl85. 1999 Int. J. Cancer. 82: 525-531.
Brian Leyland-Jones. Trastuzumab: hopes and realities. The Lancet 2002, 3: 137-144.
Cho H.S., Mason K., Ramyar K.X., Stanley A.M., Gabelli S.B., Denney D.W., Leahy D.J. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 2003,21: 756-760.
Cho H.S., Mason K., Ramyar K.X., Stanley A.M., Gabelli S.B., Denney D.W., Leahy D.J. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 2003,421:756-760.
Codony J., Albanell J., Arribas J., Baselga J.. Regulated shedding of the HER2 receptor ectodomain in human breast cancer cells. Proc. Am. Assoc. Cancer Res Annu. Meet 1999,40: 369-370.
Drebin J.A., Link V.C., Stern D.F., Weinberg RA, Greene MI. Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell 1985,41: 695- 706.
Drebin J.A., Link V.C.,Weinberg R.A,Greene MI: Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-e.ncoded tumor antigen. Proc Natl Acad Sci.USA. 1986,83: 9129 -9133.
Franklin M.C., Carey K.D., Vajdos F.F., Leahy D.J, Vos A.M, Sliwkowski M.X. Insights into ErbB2 signaling from the structure of the ErbB2-pertusumab complex. Cancer Cell 2004,5:317-327.
Franklin M.C., Carey K.D., Vajdos F.F., Leahy D.J, Vos A.M, Sliwkowski M.X. Insights into ErbB2 signaling from the structure of the ErbB2-pertusumab complex. Cancer Cell 2004,5:317-327.
Freebairn A.J.E., Last A.T.J., Illidge T.M. Trastuzumab: Designer Drug or Fashionable Fad? Clinical Oncology 2001, 13:427-433.
Harwerth I.M., Wels W., Schlegel J., Muller M., Hynes N.E.. Monoclonal antibodies directed to the erbB-2 receptor inhibit in vivo tumour cell growth. Br. J. Cancer 1993,68: 1140-1145.
Hommelgaard A.M., Lerdrup M., Van D.B. Association with membrane protrusions makes ErbB2 an internalization-resistant receptor. Mol Biol Cell 2004,15: 1557-67.
Hurwitz E., Stancovski I., Sela M., Yarden Y. Supperssion and promotion of tumor growth by monoclonal antibodies to ErbB-2 differentially correlate with cellular uptake. PNAS, 1995,92:3353-3357.
Kita Y., Tseng J., Horan T, Wen J, Philo J, Chang D, Ratzkin B, Pacifici R, Brankow D, Hu S, Luo Y, Wen D, Arakawa T, Nicolson M ErbB receptor activation, cell morphology changes, and apoptosis induced by anti-Her2 monoclonal antibodies. Biochem Biophys Res Comm 1996,226: 59
Klapper L.N., Vaisman N., Hurwitz E., Pinkaskramarski R., Yarden Y., Sela M. A subclass of tumor-inhibitory monoclonal antibodies to ErbB-2/Her2 blocks crosstalk with growth factor receptors. Oncogene 1997,14: 2099-2102.
Klapper L.N., Waterman H., Sela M., Yarden Y. Tumor-inhibitory antibodies to HER-2/ErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of HER-2. Cancer Res. 2000,60: 3384
Kumar R., Shepard H.M., Mendelsohn J. Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human mammary carcinoma cells. Mol. Cell. Biol. 1991, 11: 979-986.
Lane H.A., Motoyama A.B., Beuvink I., Hynes N.E. Modulation of p27/Cdk2 complex formation through 4D5-mediated inhibition of HER2 receptor signaling. Ann Oncol. 2001,12: S21-S22.
Le X.F., Amanda M.W., Wiener J., Wu J.Y., Mills G.B, and Bast R.C Jr. Anti-HER2 Antibody and Heregulin Suppress Growth of HER2-Overexpressing Human Breast Cancer Cells through Different Mechanisms. Clin. Cancer Res. 2000(a), 6:260-270.
Le X.F., Claret F.X., Lammayot A., Tian L., Deshpande D., Pushin R.L., Tari A.N., Bast R.C. The Role of Cyclin-dependent Kinase Inhibitor p27Kip1 in Anti-HER2 Antibody-induced G1 Cell Cycle Arrest and Tumor Growth Inhibition. J. Biol. Chem. 2003,278:23441-23450.
Le X.F., Ratna Vadlamudi, Amanda M., Bae D.S., Mills G.B., Kumar B., Bast R.C. Differential Signaling by an Anti-pl85HER2 Antibody and Heregulinl, Cancer Res. 2000(b), 60: 3522-3531.
Lee S., Yang W., Lan K.H., Sellappan S., Klos K., Hortobagyi G., Hung M.C , Yu D. Enhanced Sensitization to Taxol-induced Apoptosis by Herceptin Pretreatment in ErbB2- overexpressing Breast Cancer Cells. Cancer Res. 2002, 62:5703-5710.
Lewis Phillips GD, McMurtrey A.E., Schroeder K., Fendly B.M. Diverse activities of anti-HER2 monoclonal antibodies: from growth inhibition to induction of apoptosis. Proc Am Assoc Cancer Res. 1998, 39: 143-148.
Longva, K.E., Pedersen N.M., Haslekas, C, Stang, E., Madshus I.H. (2005) Herceptin-induced inhibition of ErbB2 signaling involves reduced phosphorlylation of Akt but not endocytic downr-egulation of ErbB2. Int. J. Cancer 116, 359-367.
Lorenzo C.D., Cozzolino R, Carpentieri A, Pucci P, Laccetti P, D'Alessio A. Biological properties of a human compact anti-ErbB2 antibody. Carcinogenesis 2005,11:1890-1895.
Lorenzo C.D., Palmer D.B., Piccoli R., Ritter M.A., D'Alession G. A new human antitumor immunoreagent specific for ErbB2. Clin. Cancer Res. 2002,8:1710-1719.
Molina, M. A. et al. Trastuzumab (Herceptin), a humanized anti-Her2 receptor monoclonal antibody inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells. Cancer Res. 2001, 61: 4744—4749.
Neve R.M., Nielsen U.B., Kirpotin D.B., Poul M.A., Marks J.D., Benz C.C. Biological Effects of Anti-ErbB2 Single Chain Antibodies Selected for Internalizing Function. Biochem. Biophys. Res. Commun. 2001,280: 274-279.
Pegram M., Hsu S., Lewis G. et al. Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene 1999,18:2241-2251.
Petit A.M., Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B, Kerbel R.S. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am.J.Pathol. 1997,151:1523
Pietras R.J., Fenly B.M., Chazin V.R., et al. Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells. Oncogene 1994,9: 1829-38
Pietras R.J., Pegram MD, Finn RS et al. Remission of human breast cancer xenografts on therapy with humanized monoclonal antibody to HER-2 receptor and DNA-reactive drugs. Oncogene 1998; 17: 2235-2249.
Pietras R.J., Poen JC, Gallardo D, Wongvipat PN, Lee HJ, Slamon DJ. Monoclonal antibody to HER-2/neu receptor modulated repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res 1999, 59: 1347-1354.
Poul, M.A., Becerril, B.,Nielsen, U.B., Morisson, P., Marks, J.D. Selection of Tumor-Specific Internalizing Human Antibodies from Phage Libraries, J. Mol. Biol. 2000,301: 1149-1161.
Sarup J.C., Johnson R.M. King K.L., Fendly B.M., Lapari M.T., Napier M.A., Ullrich A., Shepard H.M. Characterization of an anti-p185HER2 monoclonal antibody that stimulate receptor function and inhibits tumor cell growth. Growth Regul. 1: 72-77.
Sasaki S., Tsujisaki M, Jinnohara T, Ishida T, Sekiya M, Adachi M, Takahashi S, Hinoda Y, Imai K Human tumor growth suppression by apoptosis induced with anti-ErbB-2 chimeric monoclonal antibody. Jpn J Cancer Res 1998, 89:562
Shak S. Overview of the trastuzumab (Herceptin) anti-HER2 monoclonal antibody clinical program in HER2-overexpressing metastatic breast cancer. Herceptin Multinational Investigator Study Group. Semin Oncol 1999,26: 71-80.
Shawver L.K., Mann E., Elliger S.S., Dugger T.C., Arteaga C.L. Ligand-like effects induced by anti-c-erbB-2 antibodies do not correlate with and are not required for growth inhibition of human carcinoma cells. Cancer Res. 1994, 54:1367-1372.
Shawver L.K., Mann E., Elliger S.S., Dugger T.C., Arteaga C.L. Ligand-like effects induced by anti-c-erbB-2 antibodies do not correlate with and are not required for growth inhibition of human carcinoma cells. Cancer Res 1994, 54:1367
Spiridon C.I., Guinn S, Vitetta ES. A Comparison of the in Vitro and in Vivo Activities of IgG and F(ab)2 Fragments of a Mixture of Three Monoclonal Anti-Her-2 Antibodies. Clin. Cancer Res. 2004,10: 3542-3551.
Srinivas U., Tagliabue E., Campiglio M., Menard S., Colnaghi M.I., Antibody-induced activation of pl85HER2 in the human lung adenocarcinoma cell line Calu-3 requires bivalency, Cancer Immunol Immunother. 1993,36: 397-402.
Tagliabue E., Centis F., Campiglio M., Mastroianni A., Martignone S., Pellegrini R., Casalini P., Lanzi C, Menard S., Colnaghi M.I. Selection of monoclonal antibodies which induce internalization and phosphorylation of p185HER2 and growth inhibition of cells with HER2/NEU gene amplification. Int. I. Cancer 1991,47:933.
Tokuda Y./, Ohta M, Suzuki Y, Kubota M, Tajima T. Clinical development of trastuzumab in breast cancer. Breast Cancer. 2001, 8: 93-97.
Xu F., Lupu R., Rodriguez G.C., Whitaker R.S., Boente M.P., Berchuck A., Yu Y., Desombre K.A., Boyer C.M., Bast R.C. Antibody-induced growth inhibition is mediated through immunochemically and functionally distinct epitopes on the extracellular domain of the c-erbB-2 HER-2-neu gene product pl85. Int. J. Cancer 1993, 53: 401-406.
Xu F.J., Boyer CM, Bae DS, Wu S, Greenwald M, O'Briant K, Yu YH, Mills GB, Bast RC Jr. The tyrosine kinase activity of the C-erbB-2 gene product (p185) is required for growth inhibition by anti-p185 antibodies but not for the cytotoxicity of an anti-p185-ricin-A chain immunotoxin. Int. J. Cancer 1994,59:242.
Yakes F.M., Chinratanalab W. , Ritter C.A., King W., Seelig S., Arteaga C.L. Herceptin- induced Inhibition of Phosphatidylinositol-3 Kinase and Akt Is Required for Antibody-mediated Effects on p27, Cyclin D1, and Antitumor Action, Cancer Res. 2002,62: 4132-4141.
Ye D., Mendelsohn J., Fan Z. Augmentation of a humanized anti-HER2 mAb 4D5 induced growth inhibition by a human-mouse chimeric anti-EGF receptor mAb C225. Oncogene 1999,18: 731-738.
Yip L.Y., Ward R.L. (2002) Anti-ErbB2 monoclonal antibodies and ErbB2-directed vaccines. Cancer. Immunol. Immunother. 50: 569-587.
Yip Y.M., Novetny J., Edwards M., Ward R.L. Structural analysis of the ErbB2 receptor using monoclonal antibodies: Implications for receptor signaling. Int. J. Cancer 2003,104: 303-309.
Yip Y.M., Smith G., Koch J., Dubel S., Ward R. Identification of epitope regions recognized by tumor inhibitory and stimulatory anti-ErbB2 monoclonal antibodies: Implications for vaccine design. J. Immunol. 2001,166: 5271-5278.
Zhang H., Wang Q., Montone K.T., Peavey J.E., Drebin J.A., Greene M.I., Murali R. Shared Antigenic Epitopes and Pathobiological Functions of Anti-pl85her2/neu Monoclonal Antibodies. Exp. Mol. Pathol. 1999,67: 15-25.
Park BW, Zhang HT, Wu C, Berezov A, Zhang X, Dua R, et al.: Rationally designed antiher2/neu peptide mimetic disables pl85her2/neu tyrosine kinases in vitro and in vivo. Nat Biotechnol. 2000,18: 194-198.
Berezov A, Zhang HT.Greene MI, Murali R: Disabling erbb receptors with rationally designed exocyclic mimetics of antibodies: Structurefunction analysis. J Med Chem 2001,44: 2565-2574.
Azemar M., Schmidt M, Arlt F, Kennel P, Brandt B, Papadimitriou A, Groner B, Wels W. Recombinant antibody toxins specific for ErbB2 and EGF receptor inhibit the in vitro growth of human head and neck cancer cells and cause rapid tumor regression in vivo. Int J Cancer 2000; 86:269-75.
Biburger M., Weth R. Wels W.S. A Novel Bispecific Tetravalent Antibody Fusion Protein to Target Costimulatory Activity for T-cell Activation to Tumor Cells Overexpressing ErbB2/HER2. J. Mol. Biol. 2005, 346:1299-1311.
Bird R. E., Hardman KD, Jacobson JW, Johnson S, Kaufman BM, Lee SM, Lee T, Pope SH, Riordan GS, Whitlow M. Single-chain antigen-binding proteins. Science 1988, 242: 423-426.
Can Y., Suresh M. R. Bispecific antibodies as novel bioconjugates. Bioconjug. Chem. 1998, 9: 635-644.
Carter P., Presta L., Gorman C.M., Ridgway J.B., Henner D., Wong W.L., Rowland A.M., Kotts C., Carver M.E.,Shepard H.M.. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci U S A 1992; 89:,1285-4289.
Chowdhury P. S. Engineering hot spots for affinity enhancement of antibodies. Methods Mol. Biol. 2003, 207: 179-196.
Dail'Acqua W. F., Damschroder M. M., Zhang J., Woods R. M., Widjaja L. Antibody humanization by framework shuffling. Methods. 2005, 36: 43-60.
De J. J., Brissinck J, Heirman C, Demanet C, Leo O, Moser M, Thielemans K. Production and characterization of bispecific single-chain antibody fragments. Mol Immunol 1995; 32:1405-1412.
Gerstmayer B., Altenschmidt U, Hoffmann M, Wels W. Costimulation of T cell proliferation by a chimeric B7-2 antibody fusion protein specifically targeted to cells expressing the erbB2 proto-oncogene. J. Immunol. 1997, 158: 4584-4590.
Hanes J, Jermutus L, Weber-Bornhauser S, Bosshard HR, Pluckthun A. Ribosome display efficiently selects and evolves high-affinity antibodies in vitro from immune libraries. Proc Natl Acad Sci U S A 1998,95: 14130-14135.
Hanes J, Pluckthun A. In vitro selection and evolution of functional proteins by using ribosome display. Proc. Natl. Acad. Sci. 1997,94: 4937-4942.
Helguera G., Morrison S. L., Penichet M. L. Antibody-Cytokine Fusion Proteins: Harnessing the Combined Power of Cytokines and Antibodies for Cancer Therapy. Clin. Immun. 2002,105:233-246.
Ho, M., Kreitman, R. J., Onda, M., and Pastan, I. (2005) In vitro antibody evolution targeting germline hot spots to increase activity of an anti-CD22 immunotoxin. J. Biol. Chem. 280, 607-617.
Hu S, Shively L, Raubitschek A, Sherman M, Williams LE, Wong JY, Shively JE, Wu AM. Minibody: A novel engineered anti-carcinoembryonic antigen antibody fragment (single chain Fv-CH3) which exhibits rapid, high-level targeting of xenografts. Cancer Res 1996; 56:3055-3061.
Huls, G. A., Heijnen, I. A., Cuomo, M. E., Koningsberger, J. C, Wiegman, L., et al. (1999) A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments. Nat. Biotechnol. 17,276-281.
Hwang, W. Y. K., Almagro, J. C, Buss, T. N., Tan, P., and Foote, J. (2005) Use of human germline genes in a CDR homologybased approach to antibody humanization. Methods 36,35-42.
Irving R.A., Coia G., Roberts A., Nuttall S.D., Hudson P.J. Ribosome display and affinity maturation: from antibodies to single V-domains and steps towards cancer therapeutics. J. Immunol. Methods 2001,248: 31-45. Jia L. et al. Specific Tumoricidal Activity of a Secreted Proapoptotic Protein Consisting of HER2 Antibody and Constitutively Active Caspase-3. Cancer Res. 2003,63: 3257-3262.
Jones, P.T., Dear, P.H., Foote, J., Neuberger, M.S., and Winter, G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 1996, 321: 522-525.
Kashmiri, S. V., De Pascalis, R., Gonzales, N. R., and Schlom, J. SDR grafting-a new approach to antibody humanization. Methods. 2005,36: 25-34.
Knappik A., Ge, L., Honegger, A., Pack, P., Fischer, M., et al. (2000) Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs with randomized trinucleotides. J. Mol. Biol. 296, 57-86.
Le GF, Kipriyanov SM, Moldenhauer G, Little M. Di-, tri- and tetrameric single chain Fv antibody fragments against human CD19: effect of valency on cell binding. FEBS Lett 1999; 453:164-168.
Lorenzo C.D., Nigro A., Piccoli R., D'Alessio G. A new RNase-based immunoconjugate selectively cytotoxic for ErbB2-overexpressing cells. FEBS Letters 516 (2002) 208-212.
Marshall KW, Marks JD. Engineering and characterization of a novel fusion protein incorporating B7.2 and an anti-ErbB-2 single-chain antibody fragment for the activation of Jurkat T cells. J Immunother 2001; 24:27-36.
Maurer-Gebhard M, Schmidt M, Azemar M, Altenschmidt U, Stocklin E, Wels W, Groner B. Systemic treatment with a recombinant erbB-2 receptor-specific tumor toxin efficiently reduces pulmonary metastases in mice injected with genetically modified carcinoma cells. Cancer Res 1998; 58:2661-6.
McCall AM, Adams GP, Amoroso AR, Nielsen UB, Zhang L, Horak E, Simmons H, Schier R, Marks JD, Weiner LM. Isolation and characterization of an anti-CD16 single-chain Fv fragment and construction of an anti-HER2/neu/anti-CD16 bispecific scFv that triggers CD16-dependent tumor cytolysis. Mol. Immunol. 1999, 3:433-445.
Morrison, S. L., Johnson, M. J., Herzenberg, L. A., and Oi, V. T. Chimeric human antibody molecules; mouse antigenbinding antigen binding domains with human constant region domains. Proc. Natl Acad. Sci. USA 1984, 21: 6851-6855.
Reiter Y, Brinkmann U, Webber KO, Jung SH, Lee B, Pastan I. Engineering interchain disulfide bonds into conserved framework regions of Fv fragments: improved biochemical characteristics of recombinant immunotoxins containing disulfide-stabilized Fv. Protein Eng 1994; 7:697-704.
Rohrbach F, Gerstmayer B, Biburger M, Wels W. Construction and characterization of bispecific costimulatory molecules containing a minimized CD86 (B7-2) domain and single-chain antibody fragments for tumor targeting. Clin Cancer Res 2000; 6:4314-22.
Schier R, Bye J., Apell G., McCall A. Adams G.P., Malmqvist M., Weiner L.M., Marks J.D. Isolation of High-affinity Monomeric Human Anti-c-erbB-2 Single chain Fv Using Affinity-driven Selection. J. Mol. Biol. 1996,255: 28-43.
Schier, R., McCall, A., Adams, G. P., Marshall, K. W., Merritt, H., Marks J.D. Isolation of picomolar affinity anti-c-erbB-2 single-chain Fv by molecular evolution of the complementarity determining regions in the center of the antibody binding site. J. Mol. Biol. 1996,263: 551-567.
Schmidt M, McWatters A, White RA, Groner B, Wels W, Fan Z, Bast RC Jr. Synergistic interaction between an anti-p185HER-2 pseudomonas exotoxin fusion protein [scFv(FRP5)-ETA] and ionizing radiation for inhibiting growth of ovarian cancer cells that overexpress HER-2. Gynecol Oncol 2001; 80:145-55.
Skerra A, Pluckthun A. Assembly of a functional immunoglobulin Fv fragment in Escherichia coli. Science 1988; 240:1038-1041.
Tsurushita, N., Hinton, P. R., and Kumar, S. (2005) Design of humanized antibodies: from anti-Tac to Zenapax. Methods 36: 69-83.
Vaughan, T. J., Williams, A. J., Pritchard, K., Osbourn, J. K., Pope, A. R., et al. (1996) Human antibodies with subnanomolar affinities isolated from a large non-immunized phage display library. Nat. Biotechnol. 14,309-314.
Wang L, Liu B, Schmidt M, Lu Y, Wels W, Fan Z. Antitumor effect of an HER2-specific antibody-toxin fusion protein on human prostate cancer cells. Prostate 2001; 47:21-8.
Andersen D. C. Krummen L. Recombinant protein expression for therapeutic applications. Curr. Opin. Biotechnol. 2002, 13: 117-123.
Andrade E. V., Albuquerque F.C.., Moraes L.M., Brigido M.M., Santos-Silva M.A.. Single-chain Fv with Fc Fragment of the Human IgGl Tag: Construction, Pichia pastoris Expression and Antigen Binding Characterization. J. Bioehem. 2000, 128:891-895.
Brierley R.A., Davis R.G., HoItz C.G. Production of insulin-like growth factor-I in methylotrophic yeast cells. 1994. US Patent No. 5,324,639.
Brocca S., Schimidt-dannert C, Lotti M. Alberghina L, Schmid R.D. Design, total synthesis, and functional over expression of the Candida rugosa lip1 gene coding for a major industrial lipase, Protein Science, 1998, 7: 1415-1422
Byrne M.P., Titball R.W., Holley J., Smith L.A. Fermentation, Purification, and Efficacy of a Recombinant Vaccine Candidate against Botulinum Neurotoxin Type F from Pichia pastoris. Protein Expres. Purif. 2000, 18: 327-337.
Caldas C, Coelho V., Rigden D.J., Neschich G., Moro A.M., Brigido M.M. Design and synthesis of germline-based hemi-humanized single-chain Fv against the CD18 surface antigen. Protein Eng. 2000,13: 353-360.
Cereghino G.P.L., Cereghino J.L., Ilgen C, Cregg J. Production of recombinant proteins in fermenter cultures of the yeast Pichia pastoris. Curr. Opin. Biotechnol. 2002,13: 329-332.
Cereghino J.L., Cregg J.M.. Heterloguos protein expression in the methylotrophic yeast Pichia pastoris. FEMS Microbiol. Rev. 2000, 24: 45-66.
Chang H.K., Oh Y., Lee T.H. Codon optimization for high-level expression of human erythropoietin (EPO) in mammalian cells. Gene, 1997:293-301.
Cho GH, Lee DH, Min WK, Cho YJ, Kweon DH, Son DH, Park K, Seoa JH. Cloning, expression, and characterization of single-chain variable fragment antibody against mycotoxin deoxynivalenol in recombinant Escherichia coli. Protein Expres. Purif. 2004, 35: 84-92.
Clare J.J., Rayment F.B., Ballantyne S.P., Sreerkrishna K., Romanos M.A. High-level expression of tetanus toxin fragment C in Pichia pastoris strains containing multiple tandem integrations of the gene. BioTechnology 1991, 9: 455-460.
Coghlan A., Wolfe K.H . Relationship of codon bias to mRNA concentration and protein length in Saccharomyces cerevisiae. Yeast 2002,16:1131-1145.
Cupit, P.M. Whyte J.A., Porter A.J., Browne M.J., Holmes S.D., Harris W.J. Cunningham C. Clone and expression of single chain antibody fragments in Escherichia coli and Pichia pastoris. Letters Appl. Microbiol. 1999,29:273-277;
Daly R., Hearn M.T.W. Expression of heterologous proteins in Pichia pastoris: a useful experimental tool in protein engineering and production J. Mol. Recognit. 2005,18:119-138.
Damasceno L.M., Pla I., Chang H.J., Cohen L., Ritter G., Old L.J., Battc C.A., An optimized fermentation process for high-level production of a single-chain Fv antibody fragment in Pichia pastori. Protein Expres. Purif. 2004, 37: 18-26.
Delroisse J.M., Dannau M., Gilsoul J.J., Mejdoub J.E., Destain J., Portetelle D., Thonart P., Haubruge E., Vandenbol M., Expression of a synthetic gene encoding a Tribolium castaneum carboxylesterase in Pichia pastoris. Protein Expres. Purif. 2002, 42:286-294.
Eldin P., Pauza M.E., Hieda Y., Lin G., Murtaugh M.P., Pentel P.R., Pennell C.A. High-level secretion of two antibody single chain Fv fragments by Pichia pastoris. J Immunol. Methods 1997,201:67-75.
Eldin P., Pauza M.E., Hieda Y., Lin G., Murtaugh M.P., Pentel P.R., Pennell C.A. High-level secretion of two antibody single chain Fv fragments by Pichia pastoris. J. Immunol. Methods, 1997,201: 67-75.
Emberson L.M., Trivett A.J., Blower P.J., Nicholls P.J. Expression of an anti-CD33 single-chain antibody by Pichia pastoris. J. Immunol. Methods 2005, 305: 135-151.
Fischer R.. Drossard J., Emans N., Commandeur U. Hellwig S. Towards molecular farming in the future: Pichia pastoris-based production of singe-chain antibody fragments. Biotech. Appl. Biochem. 1999, 30: 117-120.
Freyre F.M., Vazquez J.E., Ayala M., Canaan-Haden L., Bell H., Rodriguez I., Gonzalez A., Cintado A., Gavilondo J.V. Very high expression of an anti-carinoembryonic antigen single chain Fv antibody fragment in the yeast Pichia pastoris. J. Biotechnol. 2000, 76: 157-163.
Goe A., Beresford G.W., Colcher D., Pavlinkova G.,Booth JM.B., Baranowska-Kortylewicz J., Batra S.K. Divalent Forms of CC49 Single-chain Antibody Constructs in Pichia pastoris: Expression, Purification, and Characterization. J. Biochem. 2000,127: 829-836.
Goel A., Colcher D., Baranowska-Kortylewicz J., Augustine S., Booth B.J., Pavlinkova G., Batra S.K. Genetically engineered tetravalent single-chian Fv of the pancarcinoma monoclonal antibody CC49: Improved biodistribution and potential for therapeutic application. Cancer Res. 2000, 60:6964-6971.
Gurkan C, Symeonides S.N, Ellar DJ. High-level production in Pichia pastoris of an anti-pl85HER-2 single-chain antibody fragment using an alternative secretion expression vector. Biotechnol Appl Biochem. 2004, 39: 115-122.
Hellwig S., Emde F., Raven N.P., Henke M., van Der Logt P., Fischer R. Analysis of single chain antibody production in pichia pastoris using on-line methanol control in fed-batch and mixed-feed fermentations. Biotechnol. Bioengineer. 2001,74: 344-352.
Hoekema A., Kastelein R.A., Vasser M., Boer H.A. Codon replacement in the PGK1 gene of Saccharomyces cerevisiae: Experimental approach to study the role of biased codon usage in gene expression. Mol. Cell. Biol. 1987, 7: 2914-2924.
Hohenblum H., Gasser B., Maurer M., Borth N., Mattanovich D. Effects of gene dosage, promoters, and substrates on unfolded protein stress of recombinant Pichia pastoris. Biotechnol. Bioeng. 2004,85: 367-375.
Hong F. Fermentation Strategies for Improved Heterlogous Expression of Laccase in Pichia pastoris, Biotechnol. Bioeng. 2002, 79(4): 438-449;
Jurado P., Ritz D., Beckwith J., Lorenzo V. Ferna'ndez L.A. Production of Functional Single-Chain Fv Antibodies in the Cytoplasm of Escherichia coli. J. Mol. Biol. 2002,320:1-10.
Kobayashi K., Kuwae S., Ohya T., et al. Addition of oleic acid increases expression of recombinant human serum albumin by the AOX2 promoter in Pichia pastoris. J Biosci Bioeng 2000,89:479-484.
Kocken C.H., Withers-Martinez C, Dubbeld M.A., Wei A., Hackett F., Valderrama A., Blackman M.J., Thomas AW. High-Level Expression of the Malaria Blood-Stage Vaccine Candidate Plasmodium falciparum Apical Membrane Antigen 1 and Induction of Antibodies That Inhibit Erythrocyte Invasion. Infect. Immunity 2002,70: 4471-4476.
Koganesawa N., Aizava T., Shimojo H., et al. Expression and purification of a small cytokine growth-blocking peptide from armyworm Pseudaletia separata by an optimized fermentation method using the methylotrophic yeast Pichia pastoris. Protein Express. Purif. 2002.25: 416-425.
Lange S., Schmitt J., Schmid R.D. High-yield expression of the recombinant, atrazine-specific Fab fragment K411B by the methylotrophic yeast Pichia pastoris, J. Immunol. Methods 2001,255: 103-114.
Li Z., Xiong F., Lin Q, et al. Low temperature increases the yield of biologically active herring antifreeze protein in Pichia pastoris. Protein Expres. Purif. 2001,21:438-445.
Liu J., Wei D., Qian F., Zhou F., Wang J., Ma Y. Han Z. pPIC9-Fc: A Vector System for the Production of Single-Chain Fv-Fc Fusions in Pichia pastoris as Detection Reagents In Vitro J. Biochem. 2003,134: 911-917.
Luo D., Geng M., Noujaim A.A., Madiyalakan R. An engineered bivalent single-chain antibody fragment that increases antigen binding activity. J. Biochem. 1996,121: 831-834.
Luo D., Mah N., Wishart D., Zhang Y., Jacobs F., Martin L. Construction and expression of bi-functional proteins of single-chain Fv with effector domains. J Biochem. 1996,120: 229-232.
Macauley-Patrick S., Fazenda M.L., McNeil B., Harvey L.M. Heterologous protein production using the Pichia pastoris expression system. Yeast. 2005,22: 249-270.
Mahiouz D.L., Aichinger G., Haskard D.O. George A.J.T. Expression of recombinant anti-E-selectin singlechain Fvantibody fragment in stably transfected insect cell lines. J Immunol Methods 1998,212: 149-160.
Marshall K.W., Marks J.D. Engineering and characterization of a novel fusion protein incorporating B7.2 and an anti-ErbB-2 single-chain antibody fragment for the activation of Jurkat T cells. J Immunother. 2001, 24: 27-36.
Marty C, Scheidegger P, Ballmer-Hofer K, Klemenz R, Schwendener RA. Production of Functionalized Single-Chain Fv Antibody Fragments Binding to the ED-B Domain of the B-isoform of Fibronection in Pichia pastoris. Protein Expres Purif. 2001,21: 156-164.
Menendez J., Hernandez L., Banguela A., Pais J. Functional production and secretion of the Gluconoacetobacter diazatrophicus fructose-releasing exo-levanase (LsdB) in Pichia pastoris. Enz. Microb. Technol. 2004.34: 446-452.
Ning D., Xiang J., Wang X., Chen., Zhang Q., Su K., Rao G., Ren X., Long Q.,Yu Z. Expression, Purification, and Characterization of Humanized Anti-HBs Fab Fragment. J. Biochem. 2004,134: 813-817.
Ogunjimi A.A., Chandler J.M., Gooding C.M., Recinos R. Choudary P.V. High-level secretory expression of immunologically active intact antibody from the yeast Pichia pastoris. Biotechnol. Letters 1999,21: 561-567.
Outchkourov N.S., Stiekema W.J., Jongsma M.A. Optimization of the Expression of Equistatin in Pichia pastoris. Protein Expres. Purif. 2002,24: 18-24.
Percudani R, Pavesi A, Ottonello S (1997) Transfer RNA gene redundancy and translation selection in Saccharomyces cerevisiae. J Mol Biol 268:322-330
Powers D.B., Amersdorfer P., Poul M.A., Nielsen U.K., Shalaby M.R., Adams G.P., Weiner L.M., Marks J.D. Expression of single-chian Fv-Fc fusions in Pichia pastoris. J. Immunol. Methods 2001,251: 123-135.
Rahbarizadeh F., Rasaee M.J. Forouzandeh M., Allameh A.A. Over expression of anti-MUCl single-domain antibody fragments in the yeast Pichia pastoris Mol. Immunol. 2006,43:426-435.
Raju T.S., Briggs J., Borge S.M., Jones A.J.S. Species-specific variation in glycosylation of IgG: evidence for the species-specific sialylation and branch-specific galactosylation and importance for engineering recombinant glycoprotein therapeutics. Glycobiol. 2000,10:477-486.
Richard L.B. Milek, Hendrik G. Stunnenberg, Ruud N.H. Konings. Assembly and expression of a synthetic gene encoding the antigen Pfs48/45 of the human malaria parasite Plasmodium falciparum in yeast. Vaccine 2000, 18: 1402-1411.
Ridder R., Schmitz R., Legay F., Gram H. Generation of rabbit monoclonal antibody fragments from a combinatorial phage display library and their production in the yeast Pichia pastoris. Biotechnology 1995,13: 255-260.
Ridder R.,et al, Generation of rabbit monoclonal antibody fragments from a combinational phage display library and their production in the yeast. Biotechnol. 1995,13:255-260.
Sarramegna V., Demange P., Milon A., Talmont F. Optimizing Functional versus Total Expression of the Human u-Opioid Receptor in Pichia pastoris, Protein Expres. Purif. 2002,24:212-220.
Sharp P.M, Tuohy T., Mosurski K.R. Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucl. Acids Ras. 1986, 14.
Sharp P.M., Cowe E. (1991) Synonymous codon usage in Saccharomyces cerevisiae. Yeast 7:657-678
Sharp P.M., Li W.H. The codon adaptation index - a measure of directional synonymous codon usage bias, and its potential applications. Nucl. Acids Res. 1987,15:1281-1295.
Sharp P.M., Stenico M., Peden J.F., Lloyd A.T. Codon usage: mutational bias, translational selection, or both? Biochemistry Society Trans. 1993,21: 835-846.
Shi X., Karkut T., Chamankhah M., et al. Optimal conditions for the expression of a single-chain antibody (scFv) gene in Pichia pastoris. Protein Expres. Purif. 2003, 28:321-330.
Shinkawa, T., Nakamura, K., Yamane, N., Shoji-Hosaka, E., Kanda, Y. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgGl complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J. Biol, Chem. 2003, 278: 3466-3473.
Sinclair G. Synonymous codon usage bias and the expression of human glucocerebrosidase in the methylotrophic yeast Pichia pastoris. Protein Expres. Purif. 2002, 26: 96-105.
Sinclair G., Choy F. Synonymous codon usage bias and the expression of human glucocerebrosidase in the methylotrophic yeast Pichia pastoris. Protein Expres. Purif. 2002, 26: 96-105.
Sreekrishna K. Strategies for optimizing protein expression expression and secretion in the methylotrophic yeast Pichia pastoris, in "Industrial Microorganisms: Basic and Applied Molecular Genetics". Am. Soc. Microbiol., Washington, DC. 1993: 19-126.
Sreekrishna K., Brankamp R. G., Kropp K. E., Blankenship D. T., Tsay J.T., Smith P.L., Wierschke J.D., Subramaniam A., Birkenberger L.A. Strategies for optimal synthesis and secretion of heterloguos proteins in the methylotrophic yeast Pichia pastoris. Gene 1997, 190: 55-62.
Vassileva A., Chugh D.A., Swaminathan S., Khanna N. Effect of Copy Number on the Expression Levels of Hepatitis B Surface Antigen in the Methylotrophic Yeast Pichia pastoris. Protein Expres. Purif. 2001, 21: 71-80.
Venturi M., Seifert C., Hunte C., High Level Production of Functional Antibody Fab Fragments in an Oxidizing Bacterial Cytoplasm. J. Mol. Biol. 2002, 315: 1-8.
Wang Y., Wang K., Jette D.C., Wishart D.S. Production of an anti-prostate-specific antigen single-chain antibody fragment form Pichia pastoris. Protein Expres. Purif. 2001, 23: 419-425.
Wolff A.M., Hansen O.C., Poulsen U., Madrid S., Stougaard P. Optimization of the Production of Chondrus crispus Hexose Oxidase in Pichia pastoris. Protein Expres. Purif. 2001, 22: 189-199.
Woo J. H., Liu Y.Y., Mathias A, Stavrou S., Wang Z., Thompson J., Neville D.M. Gene optimization is necessary to express a bivalent anti-human anti-T cell immunotoxin in Pichia pastoris, Protein Expres. Purif. 2002, 25: 270-282.
Woo J. H., Liu Y. Y., Stavrou S., Neville D.M., Increasing Secretion of a Bivalent Anti-T-Cell Immunotoxin by Pichia pastoris. Appl. Environ. Micorbiol. 2004, 70: 3370—3376.
Xia X. How Optimized Is the Translational Machinery in Escherichia coli, Salmonella typhimurium and Saccharomyces cerevisiae? Genetics 149: 37-44 (May, 1998)
Xia X. Maximizing Transcription Efficiency Causes Codon Usage Bias. Genetics 1996, 144: 1309-1320.
Zhang Z, Zhi-Hua Li, Fei Wang, Min Fang, Chang-Cheng Yin, Zhi-Yong Zhou, Qing Lin, and Hua-Liang Huang. Overexpression of DsbC and DsbG markedly improves soluble and functional expression of single-chain Fv antibodies in Escherichia coli. Protein Expres. Purif. 2002, 26: 218-228.
贝锦龙等．人工合成黑曲霉基因NRRL3135菌株植酸酶基因在毕赤酵母系统中的高效表达．生物工程学报，2001，17：254-258．
黄秉仁等．人工合成表皮生长因子基因在甲基营养型酵母中的高效表达．中国生化与分子生物学报．1998，14：512-517．
姚斌，张春义，王建华．高效表达具有生物学活性植酸酶．中国科学C辑．1998，14．
赵翔，霍克克，李育阳．毕赤酵母密码子用法分析．生物工程学报．2000，16．
Atoda H., Ishikawa M., Mizuno H., Morita T., 1998. Coagulation Factor X-Binding Protein from Deinagkistrodon acutus venom is a Gla domain-binding protein. Biochemistry 37, 17361-17370.
Atoda H., Kaneko H., Mizuno H., Morita T. Calcium-binding analysis and molecular modeling reveal echis coagulation factor IX/factor X-binding protein has the Ca-binding properties and Ca ion-independent folding of other C-type lectin-like proteins. FEBS Letters 2002, 531: 229-234.
Atoda, H., Ishikawa, M., Yoshihara, E., Sekiya, F., Morita, T., 1995. Blood coagulation factor Ⅸ-binding protein from the venom of Trimeresurus flavoviridis: purification and characterization. J. Biochem. 118, 965-973.
Drickamer, K. C-type lectin-like domains. Curr. Opin. Struet. Biol. 1999, 9: 585-590.
Li W. F., Chen L., Li X.M., Liu J. A C-type lectin-like protein from Agkistrodon acutus venom binds to both platelet glycoprotein Ib and coagulation factor Ⅸ/factor. Biochem. Biophys. Res. Commun. 2005, 332: 904-912.
Lu Q., Navdaev A., Clemetson J.M., Clemetson K.J. Snake venom C-type lectins interacting with platelet receptors. Structure-function relationships and effects on haemostasis. Toxicon 2005,ⅩⅩ:1-10.
Mizuno H., Fujimoto Z., Atoda H., Morita T. Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X. Proc. Nat. Acad. Sci. 2001, 98: 7230-7234.
Morita.T. Structures and functions of snake venom CLPs (C-type iectin-like proteins) with anticoagulant-, procoagulant-, and platelet-modulating activities. Toxicon 2005, 45: 1099-1114.
Myers D. D., Wakefield T.W. Inflammation-Dependent Thrombosis. Front. Bioscience 2005, 10: 2750-2757.
Ogawaa T., Chijiwab T., Uedab K.O., Ohno M. Molecular diversity and accelerated evolution of C-type lectin-like proteins from snake venom. Toxicon 2005, 45: 1-14.
Paaventhan P., Kong C, Joseph J.S., Chung M.C., Kolatkar P.R. Structure of rhodocetin reveals noncovalently bound heterodimer interface. Protein Science 2005,4: 169-175.
Tani A., Ogawa T., Nose T., Nikandrow N.N., Deshimaru M., Chijiwa T., Chang C.C., Fukumaki Y., Ohno M., 2002. Characterization, primary structure and molecular evolution of anticoagulant protein from Agistrodon actus venom. Toxicon 40, 803-813.
Xu X.L., Liu Q.L., 2001. Binding of anticoagulation factor II from the venom of Agkistrodon acutus with activated coagulation factor X. Toxicon. 39: 1359-1365.
Xu X.L., Liu Q.L., Xie Y.Sh, Wu Sh.D., 2000. Purification and characterization of anticoagulation factors from the venom of Agkistrodon acutus. Toxicon 38,1517-1528.
Yu H., Xiang K., Wang Y., Liu J., 2003. Cloning and sequencing of eleven cDNAs of C-type lectin-like protein subunits from Agkistrodon Acutus. Chinese Journal of Biochemistry and Molecular Biology 19(1), 64-70.
Beatty J. D., Beatty B.G., Vlahos W.G. Measurement of monoclonal antibody affinity by non-competitive enzyme immunoassay. J. Immunol. Methods 1987, 26: 173-179.
Brocca S., Schmidt-Dannert C., Lotti M., Alberghinaand L., Schmid R.D. Design, total synthesis, functional overexpression of the Candida rugosa lip 1 gene coding for a major industrial lipase. Protein Sci. 1998, 7: 1415-1422.
Chen L. S., Liu A. P., Liu. J. Construction, expression and characterization of the engineered antibody against tumor surface antigen P185~(c-erbb-2). Cell Res. 2003, 13: 35-48.
Daly R., Hearn M. T. W. Expression of heterologous proteins in Pichia pastoris: a useful experimental tool in protein engineering and production. J. Mol. Recognit. 2005, 18:119-138.
Herrick D., Parker R., Jacobson A. Identification and comparison of stable and unstable mRNAs in Saccharomyces cerevisiae. Mol. Cell. Biol. 1990, 10: 2269-2284.
Hoekema A., Kastelein R. A., Vasser M., Boer H.A. Codon replacement in the PGK1 gene of Saccharomyces cerevisiae: experimental approach to study the role of biased codon usage in gene expression. Mol. Cell. Biol. 1987, 7: 2914-2924.
Hohenblum H., Gasser B., Maurer M., Borth N., Mattanovich D. Effects of Gene Dosage, Promoters, and Substrates on Unfolded Protein Stress of Recombinant Pichiapastoris. Biotechnol. Bioeng. 2004, 85: 367-375.
Kauffman K. J., Pridgen E. M., Doyle F. J., Dhurjati P. S., Robinson A.S. Decreased protein expression and intermittent recoveries in BiP levels result from cellular stress during heterologous protein expression in Saccharorayces cerevisiae. Biotechnol. Prog. 2002, 18: 942-950.
Kim C. H., Younghoon O., Lee T. H. Codon optimization for high-level expression of human erythropoietin (EPO) in mammalian cells. Gene 1997, 199: 293-301.
Li P., Li Y., Wang C., Liu J. Investigation on anti-cancer activities of anti-P185 monoclonal antibodies in vitro. Chinese J. Immunol. 2002, 18: 33-35.
Li, P., Li, Y., Wang, C., Liu, J. (2003) Characterization and utilization of twon novel anti-ErbB2 monoelonal antibodies in detection of soluble ErbB-2 for breast cancer prognosis.
Liu S. H., W. I. Choua, C.C. Sheub, Changa M.D. Improved secretory production of glucoamylase in Pichia pastoris by combination of genetic manipulations. Biochem. Biophys. Res. Commun. 2005, 326:817-824.
Oliveira C.C., Heuvel J.J., McCarthy J.E.G. Inhibition of translational initiation in Saccharomyces cerevisiae by secondary structure: the roles of the stability and position of stem-loops in the mRNA leader. Mol. Microbiol. 1993, 9: 521-532.
Outchkourov N. S., Stiekema W.J., Jongsma M. A. Optimization of the Expression of Equistatin in Pichia pastoris, Protein Expres. Purif. 2002, 24: 18-24.
Prodromou C., Pearl L. H. Recursive PCR: a novel technique for total gene synthesis. Protein Eng. 1992, 8: 827-829.
Powers D. B., Amersdorfer P., Poul M. A., Nielsen U.K., Shalaby M.R., Adams G.P., Weiner L.M., Marks J.D. Expression of single-chian Fv-Fc fusions in Pichia pastoris. J. Immunol. Methods 2001, 251: 123-135.
Seffens W., Digby D. mRNAs have greater negative folding free energies than shuffled or codon choice randomized sequence. Nucl. Acids Res. 1999, 27: 1578-1584.
Shi X., Karkut T., Chamankahh M., Alting M.M., Hemmingsen S.M., Hegedus D. Optimal conditions for the expression of a single-chain antibody (scFv) gene in Pichia pastoris. Protein Expres. Purif. 2003, 28:321-330.
Shusta E.V., Raines R. T., Pluckthun A, Wittrup K. D. Increasing the secretory capacity of Saccharomyces cerevisiae for production of single-chain antibody fragments. Nat. Biotechnol. 1998, 16: 773-778.
Sinclair G., Choy F. Y. M. Synonymous codon usage bias and the expression of human glucocerebrosidase in the methylotrophic yeast Pichiapastors. Protein Expres. Purif. 2002, 26: 96～105.
Sreekrishna K., R. G. Brankamp, K. E. Kropp, D. T. Blankenship, J. T. Tsay, P. L. Smith, J.D. Wierschke, A.
Subramaniam, L.A. Birkenberger, Strategies for optimal synthesis and secretion of heterologous proteins in the methylotrophic yeast Pichia pastoris. Gene 1997,190: 55-62.
Vad R., E. Nafstad, L.A. Dahl, Gabrielsen O.S. Engineering of a Pichia pastoris expression system for secretion of high amounts of intact human parathyroid hormone. J. Biotechnol. 2005,30:251-260.
Wang J., Shi Y., Liu Y., Hu S., Ma J., Liu J., Chen L. Purification and characterization of a single-chain chimeric anti-pl85 antibody expressed by CHO-GS system. Protein Expres. Purif. 2005,41: 68-76.
Wolff A.M., Hansen O.C., Poulsen U., Madrid S., Stougaard P. Optimization of the production of chondrus crispus hexose oxidase in P. pastoris. Protein Expres. Purif. 2001,22: 189-199.
Woo Y., Liu Y., Mathias A., Stavrou v, Wang Z., Thompson J., Neville D.M. Gene optimization is necessary to express a bivalent anti-human anti-T cell immunotoxin in Pichia pastoris. Protein Expres. Purif. 2002, 25: 270-282.
Xia X. How optimized is the translational machinery in Escherichia coli, Salmonella typphimuriu and Saccharomyces cerevisiae? Genetics 1998,149: 37-44.
Zhao X., K.K. Huo, Li Y. Y. Synonymous codon usage in Pichia pastoris. Chinese J. Biotechnol. 2000,16: 308-311.
Almagro, J. C. (2004) Identification of differences in the specificity-determining residues of antibodies that recognize antigens of different size: implications for the rational design of antibody repertoires. J. Mol. Recognit. 17, 132-143.
Baselga, J., Albanell, J. Mechanism of action of anti-HER2 monoclonal antibodies. Ann. Oncol. Suppll (2001) 35-41.
Bell, C. A., Tynan, J. A., Hart, K.C., Meyer, A.N., Robertson, S.C., Donoghue, D.J. (2002) Rotational Coupling of the Transmembrane and Kinase Domains of the Neu Receptor Tyrosine Kinase. Mol. Biol. Cell. 11, 3589-3599
Bissan A. L., Arthur M. L., Cyrus C., Standard conformations for the canonical structures of immunoglobulins, J. Moi. Bio. 1997, 273: 927-948.
Boyer, C.M., Pusztai, L., Wiener, J. R., Xu, F. J., Dean, G.S, Bast, B.S., O'Briant, K.C., Greenwald, M., Desombere, K.A., Bast, R.C. (1999) Relative cytotoxic activity of immunotoxins reactive with different epitopes on the extracellular domain of the c-erbb-2 (her-2/neu) gene product p185. Int. J. Cancer. 82, 525-531.
Braden, B. C., Poljak, B.J. (1995) Structural features of the reactions between antibodies and protein antigens. FASEB J. 9, 9-16.
Bruniger, A. T., Rice, L.M., (1997) Crystallographic refinement by simulated annealing: methods and applications. Chao G., Cochran J.R., Wittrup K.D., Fine epitope mapping of anti-epidermal growth factor receptor antibodies through random mutagenesis and yeast surface display, J. Mol. Bio., 2004 342, 539-550.
Cho H. S., Mason K., Ramyar K. X., Stanley A. M., Gabelli S. B., Dermey D.W., Leahy D.J., Structure of the extraceilular region of HER2 alone and in complex with the Herceptin Fab, Nature, 2003, 421: 756-760.
Conte, L. L., Chothia, C., Janin, J. (1999) The Atomic Structure of Protein-Protein Recognition Sites. J. Mol. Biol. 285, 2177-2198.
David, R. D., Gerson, H.C. (1996) Interactions of protein antigens with antibodies. Proc. Natl. Acid. Sci. 93, 7-12.
Decanniere, K., Muyldermans, S., Wyns, L. (2000) Canonical Antigen-binding Loop Structures in Immunoglobulins: More Structures, More Canonical Classes? J. Mol. Biol. 300: 83-91.
Franklin M. C., Carey K. D., Vajdos F. F., Leahy D. J, Vos A.M, Sliwkowski M.X., Insights into ErbB2 signaling from the structure of the ErbB2-pertusumab complex. Cancer Cell, 2004, 5:317-327.
Itoh K., Inoue K., Tezuka T., Tada H., Hashimoto Y., Masuko T., Suzuki T., Molecular structual and funtional characterization of tumor suppressive anti-ErbB2 monoclonal antibody by phage display system, J. Biochem., 2003, 133: 239-245.
Jones, T. A., Kjeldgaard, M. (1997) Electron-density map interpretation, Methods Enzymol. 277,173-208.
Klapper, L.N., Vaisman, N., Hurwitz E., Ronit P.K, Yarden Y., Sela, M. A subclass of tumor-inhibitory monoclonal antibodies to ErbB-2/HER blocks crosstalk with growth factor receptors. Oncogene (1997) 14, 2099-2109.
Laskowski, R.A., MacArthur, M.W., Moss, D.S., Thornton, J.M. (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26,283-291.
Le X.F., Amanda M.W., Wiener J., Wu J.Y., Mills G.B., and Bast R.C Jr. Anti-HER2 Antibody and Heregulin Suppress Growth of HER2-Overexpressing Human Breast Cancer Cells through Different Mechanisms. Clin. Cancer Res. 2000,6: 260-270.
L Li, H. Liu, S. Hu, D. Liang, L. Cheng, J. Liu. Soluble Expression and Characterization of Disulfide Bond-rich Subdomains of membrane Protein p 185 in E. coli. Chinese Journal of Biotechnology 2005,21: 590-596.
Longva, K.E., Pedersen N.M., Haslekas, C, Stang, E., Madshus I.H. (2005) Herceptin-induced inhibition of ErbB2 signaling involves reduced phosphorlylation of Akt but not endocytic downr-egulation of ErbB2. Int. J. Cancer 116, 359-367.
Lorenzo, C.D., Palmer, D.B., Piccoli R., Ritter M.A., D'Alession G. (2002) A new human antitumor immunoreagent specific for ErbB2. Clin. Cancer Res. 8,1710-1719.
Neve R.M., Nielsen U.B., Kirpotin D.B., Poul M.A., Marks J.D., Benz C.C. Biological Effects of Anti-ErbB2 Single Chain Antibodies Selected for Internalizing Function, Biochem. Biophys. Res. Commun. 280 (2001) 274-279.
Otwinowski, Z., Mior W. (1997) Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326.
Ritchie, R.W. (2003) Evaluation of protein docking predictions using Hex 3.1 in CAPRI rounds 1 and 2. Proteins: Struc. Func. Bioinform. 52, 98-106.
Vajda, S., Camacho, C.J. Protein-protein docking: is the glass half-full or half-empty? (2004) Trends. Biotech. 22, 111-116.
Veronica M., Anna T., Mauro R., Cyrus C, Arthur M.L, Conformations of the third hypervariable region in the VH domain of immunoglobulins, J. Mol. Bio., 1998,275: 269-294.
Yip Y.M., Novetny J., Edwards M., Ward R.L., Structural analysis of the Erbb2 receptor using monoclonal antibodies: Implications for receptor signaling, Int. J. Cancer 2003,104: 303-309.
Yip, Y.M., Smith, G., Koch, J., Dubel, S., Ward, R. (2001) Identification of epitope regions recognized by tumor inhibitory and stimulatory anti-ErbB2 monoclonal antibodies: Implications for vaccine design. J. Immuno. 166, 5271-5278.
Yum, L.Y., Robyn, L.W. Anti-ErbB2 monoclonal antibodies and ErbB2-directed vaccines. (2002) Cancer. Immunol. Immunother. 50,569-587.
Arocas, V., Castro, H. C., Zingali, R. B, Guillin, M. C, Martin, J. P, Bon, C., Wisner, A., 1994. Molecular cloning and expression of bothrojaracin, a potent thrombin inhibitor from snake venom. European Journal of Biochemistry 248, 550-557.
Atoda, H., Ishikawa, M., Mizuno, H., Morita, T., 1998. Coagulation Factor X-Binding Protein from Deinagkistrodon acutus venom is a Gin domain-binding protein. Biochemistry 37, 17361-17370.
Atoda, H., Ishikawa, M., Yoshihara, E., Sekiya, F., Morita, T., 1995. Blood coagulation factor Ⅸ-binding protein from the venom of Trimeresurusflavoviridis: purification and characterization. Journal of Biochemistry 118, 965-973.
Atoda, H., Yoshida, N., Ishikawa, M., Morita, T., 1994. Binding properties of the coagulation factor Ⅸ/factor Ⅹ-binding protein isolated from the venom of Trimeresurus flavoviraids, European Journal of Biochemistry, 224, 703-708.
Chen Y. L.,Tsai I. H. Functional and sequence Characterization of agkice2 tin, a new glycoprotein Ib antagonist isolated from Agkistrodon acutus venom. Biochem. Biophys. Res. Commun. 1995, 210: 472-477.
Chen, Y. L. and Tsai, I. H., 1996. Functional and Sequence Characterization of Coagulation Factor Ⅸ/Factor
Cheng X., Qian Y., Liu Q., Benjamin X.Y. Lid, Zhang M., Liu J. Purification, Characterization, and cDNA Cloning of aNew Fibrinogenlytic Venom Protein, Agkisacutacin from Agkistrodon acutus Venom. Biochem. Biophys. Res. Commun. 1999, 265: 530-535.
Cregg, J. M., Cereghino, J.L., Shi, J, Higgins, D.R., 2000. Recombinant protein expression in Pichia pastoris. Molecular Biotechnology 16(1), 23-52.
Diacovo T. G., Liddingtonl R.C., Fukuda K., Dogger T.A., Bankston L.A. Cruz M.A. Structural Basis of von Willebrand Factor Activation by the Snake Toxin Botrocetin. Structure 2002, 10: 943-950. Horii K., Okuda D., Morita T., Mizuno H. Crystal Structure of EMS16 in Complex with the Integrin a2-I Domain. J. Mol. Biol. 2004, 341: 519-527.
Fidler, S.L., Young, W., McNatty, K.P., 1998. Expression and secretion of a biologically active glycoprotein hormone, ovine follicle stimulating hormone by Pichia pastoris. Journal of Molecular Endocrinology 21,327-336.
Fukuda, K., Mizuno, H., Atoda, H., Morita, T., 2000. Crystal Structure of Flavocetin-A, a Platelet Glycoprotein Ib-Binding Protein, Reveals a Novel Cyclic Tetramer of C-Type Lectin-like Heterodimers. Biochemistry 39, 1915-1923.
Hirotso, S., Mizuno, H., Fukuda, K., Qi, M.C., Matsui, T., Hamako, J., Morita, T., Titani, K., 2001. Crystal Structure of Bitiscetin, avon Willebrand Factor-Dependent Platelet Aggregation Inducer. Biochemistry 40, 13592-13597.
Jasti, J., Paramasivam, M., Srinivasan, A., Singh, T. P., 2004. Crystal structure of echicetin from Echis carinatus (Indian saw-scaled viper) at 2.4 A° resolution. Journal of Molecular Biology 335, 167-176.
Kalandadze, A., Galleno, M., Foncerrada, L., Strominger, J.L., Wucherpfennig, K.W., 1996. Expression of recombinant HLA-DR.2 molecules: Replacement of the hydrophobic transmembrane region by a leucine zipper dimerization motif allows the assembly and secretion of soluble DR alpha beta heterodimers. Journal of Biological Chemistry 271,20156-20162.
Kawasaki, T., Fujimura, Y., Usami, Y., Suzuki, M., Miura, S., Sakurai, Y., Makita, K., Taniuchi, Y., Hirano, K., Titani, K., 1996. Complete amino acid sequence and identification of the platelet glycoprotein Ib-binding site of jararaca GPIb-BP, a snake venom protein isolated from Bothrops jararaca. Journal of Biological Chemistry 271, 10625-10639.
Lange, S., Schmitt, J., Schmid, R.D., 2001. High-yield expression of the recombinant, atrazine-specific Fab fragment K411B by the methylotrophic yeast Pichia pastoris. Journal of Immunological Methods 255,103-114.
Lee, W.H., Zhuang, Q.Y., Zhang, Y., 2003. Cloning and characterization of a blood coagulation factor IX-binding protein from the venom of Trimeresurus stejnegeri. Toxicon 41, 765-772
Li W., Chen L., Li X., Liu J. A C-type lectin-like protein from Agkistrodon acutus venom binds to both platelet glycoprotein Ib and coagulation factor IX/factorX. Biochem. Biophys. Res. Commun. 2005, 332: 904-912.
Li X., Ji H., Cheng X., Banjamin X.Y. Lid, Ng T.B. Antithrombotic and thrombolytic activities of Agkisacutacin, a snake venom proteinase, in experimental models. General Pharmac. 2002, 35: 179-187.
Lu, Q., Navdaev, A., Clemetson, J.M., Clemetson, K.J., 2005. Snake venom C-type lectins interacting with platelet receptors. Structure-function relationships and effects on haemostasis. Toxicon (in press).
Maita N., Nishio K., Nishimoto E., Matsui T., Shikamoto Y., Morita T., Sadler J.E., Mizuno H. Crystal Structure of von Willebrand Factor Al Domain Complexed with Snake Venom, Bitiscetin: Insight Into Glycoprotein Ib Binding Mechanism Induced By Snake Venom Proteins, J. Biol. Chem. 2003,39: 37777-37781.
Mizuno, H., Fujimoto, Z., Atoda, H., Morita, T., 2001. Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X. Proceedings of the National Academy of Science 98 (13), 7230-7234.
Mizuno, H., Fujimoto, Z., Koizumi, M., Kano, H., Atoda, H., Morita, T., 1997. Structure of coagulation factors IX/X-binding protein, a heterodimer of C-type lectin domains. Nature Structure Biology 4,438-441.
Mizuno, H., Fujimoto, Z., Koizumi, M., Kano, H., Atoda, H., Morita, T., 1999. Crystal structure of coagulation factor IX-binding protein from Habu snake venom at 2.6 A: implication of central loop swapping based on deletion in the linker region. Journal of Molecular Biology 289,103-112.
Monteiro, R.Q, Foguel, D., Castro, H.C., Zingali, R.B., 2003. Subunit dissociation, unfolding, and inactivation of bothrojaracin, a C-type lectin-like protein from snake venom. Biochemistry 42, 509-515.
Morita, T., 2004. Use of snake venom inhibitors in studies of the function and tertiary structure of coagulation factors. International Journal of Hematology 79,123-129.
Ogawa, T., Chijiwa, T., Oda-Ueda, N., Ohno, M., 2005. Molecular diversity and accelerated evolution of C-type lectin-like proteins from snake venom. Toxicon 45,1-14.
Ogunjimi, A.A., Chandler, J.M., Gooding, C.M., 1999. High-level secretory expression of immunologically active intact antibody from the yeast Pichia pastoris. Biotechnology Letters 21, 561-567.
Paaventhan, P., Kong, C, Joseph, J.S., Chung, M.C., Kolatkar, P.R., 2005. Structure of rhodocetin reveals noncovalently bound heterodimer interface. Protein Science 4(1), 169-175.
Peng, M., Holt, J.C., Niewiarowski, S., 1994. Isolation, characterization and amino acid sequence of echicetin b subunit, a specific inhibitor of von willebrand factor and thrombin interaction with glycoprotein Ib. Biochemical and Biophysical Research Communications 205(1), 68-72.
Polgar, J., Magnenat, E.M., Peitsch, M.C., Wells, T.N., Saqi, M.S., Clemetson, K.J., 1997. Amino acid sequence of the alpha subunit and computer modeling of the alpha and beta subunits of echicetin from the venom of Echis carinatus (saw-scaled viper). Biochemical Journal 15(323), 533-537.
Richard, F., Robert, P., Remy, J.J., Martinat, N., Bidart, J.M., Salesse, R., Combarnous, R., 1998. High-level secretion of biologically active recombinant porcine follicle-stimulating hormone by the methylotrophic yeast Pichia pastoris Biochemical and Biophysical Research Communications 245,847-852.
Sen, U., Vasudevan, S., Subbarao, G., McClintock, R.A., Celikel, R., Ruggeri, Z.M., Varughese, K.I, 2001. Crystal structure of the von Willebrand factor modulator botrocetin, Biochemistry 40,345-352.
Sreekrishna, K., Brankamp, R.G., Kropp, K.E., Blankenship, D.T., Tsay, J.T., Smith, P.L., Wierschke, J.D., Subramaniam, A., Birkenberger, L.A., 1997. Strategies for optimal synthesis and secretion of heterologous proteins in the methylotrophic yeast Pichia pastoris. Gene 190,55-62.
Tani, A., Ogawa, T., Nose, T., Nikandrow, N.N., Deshimaru, M., Chijiwa, T., Chang, C.C., Fukumaki, Y., Ohno, M., 2002. Characterization, primary structure and molecular evolution of anticoagulant protein from Agistrodon actus venom. Toxicon 40,803-813.
Wang W.J., Huang T.F.. A novel tetrameric venom protein, agglucetin from Agkistrodon acutus, acts as a glycoprotein Ib agonist. Thromb. Haemost. 2001,86:1077-1186.
X-Binding Protein from the Venom of Echis carinatus leucogaster. Biochemistry 35, 5264-5271.
Xu G., Ulrichts H., Vauterin S., Meyer S., Deckmyn H., Teng M., Niu L. How does agkicetin-C bind on platelet glycoprotein Iba and achieve its platelet effects? Toxicon 2005,45: 561-570.
Xu, X.L., Liu, Q.L., 2001. Binding of anticoagulation factor II from the venom of Agkistrodon acutus with activated coagulation factor X. Toxicon 39,1359-1365.
Xu, X.L., Liu, Q.L., Xie, Y.Sh., Wu, Sh.D., 2000. Purification and characterization of anticoagulation factors from the venom of Agkistrodon acutus. Toxicon 38, 1517-1528.
Yu, H., Xiang, K., Wang, Y., Liu Jo, 2003. Cloning and sequencing of eleven cDNAs of C-type lectin-like protein subunits from Agkistrodon Acutus. Chinese Journal of Biochemistry and Molecular Biology 19(1), 64-70.
刘四九博士论文，2000，皖南尖吻蝮蛇蛇毒抗凝蛋白ACFI-Ⅰ和ACF-2结构与功能关系的研究。
朱忠良博士论文，2003，皖南尖吻蝮蛇蛇毒丝氮酸蛋白酶AaV-SP-Ⅰ和AaV-SP-Ⅱ及蛇毒C性凝集素类似蛋白agkaggrengin，AaACP-A-analogue和AaACP-B-analogue的结构生物学研究。
Borg JP, Marchetto S, Le Bivic A, Ollendorff V, Jaulin-Bastard F, Saito H, Foumier F, Adelaide J, Margolis B, Birnbaum D. ERBIN: abasolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor. Nat Cell Biol 2002: 407-414.
Burgess A. W., Cho H. S., Eigenbrot, K., Ferguson, K.M., Thomas P.J. Garrett, Leahy D.J., Lemmon, M. A.,Siiwkowski, M.X, Ward, C.W, Yokoyama, S. An open-and-shut case? Review recent insights into the activation of EGF/ErbB receptors. Mol. Cell. 2003, 12: 541-552.
Camenisch T.D., Schroeder J.A, Bradley J., Klewer S.E., Mcdonald J.A. Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2-ErbB3 receptors. Nat. Medicine 2002, 8: 850-855.
Cho H.S., Mason K., Ramyar K.X., Stanley A.M., Gabelli S.B., Denney D.W., Leahy D.J. (2003) Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421: 756-760.
Claesson-Welsh L. Signal transduction by receptor tyrosine kinases. Toxicol. Vitro. 1998, 12: 525-536.
Coussens L., Yang-Feng T.L., Liao Y.C., Chen E., Gray A., McGrath J., Seeburg P.H., Libermann T.A., Schlessinger J., Francke U., Levinson A., Ullrich A. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 1985,230: 1132-1139.
Franklin M.C., Carey K.D., Vajdos F.F., Leahy D.J, Vos A.M, Sliwkowski M.X. Insights into ErbB2 signaling from the structure of the ErbB2-pertusumab complex. Cancer Cell 2004,5: 317-327.
Garratt A.N., Ozcelik C, Birchmeier C. ErbB2 Pathways in Heart and Neural Diseases. Trends Cardiovasc. Med. 2003,13: 80-86.
Graus-Porta D., Beerli R.R., Daly J.M., Hynes N.E. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. The EMBO J. 1997,16:1647-1655.
Hommelgaard A.M., Lerdrup M., Van Deurs B. Association with membrane protrusions makes ErbB2 an intemalization-resistant receptor. Mol Biol Cell 2004, 15: 1557-67.
Hynes N.E., Horsch K., Olayioye M.A., Badache A. The ErbB receptor tyrosine family as signal integrators. Endocrine-Related Cancer 2001, 8: 151-159.
Jaulin-Bastard F, Saito H, Le Bivic A, Ollendorff V, Marchetto S, Birnbaum D, Borg JP. The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins. J Biol. Chem. 2001, 276: 15256-15263.
Lidke D.S., Nagy P., Heintamann R., Arndt-Jovin D., Post J.N., Grecco H.E., Jares-Erijman E.A., Jovin T.M. Quantum dot ligands provide new insights into erbB/Her receptor-mediated signal transduction. Nat. Biotechnol. 2004, 22: 198-203.
Marmor M.D., Skaria K.B., M. Sc, Yarden Y. Signal Transduction And Oncogenesis By Erbb/Her Receptors. Int. J. Radiation Oncol. 2004, 58: 903-913.
Nancy E.H., Heidi A., Lane N. Erbb receptors and cancer: the complexity of targeted inhibitors Nat. Rev. Cancer 2005,5: 341-354.
Olayioye M.A., Neve R.M., Lane H.A., Hynes N.A. The ErbB signaling network: receptor heterodimerization in development and cancer, The EMBO J. 2000,19: 3159-3167.
Olayioye M.A., Neve R.M., Lane, H.A. Hynes H.E. The ErbB signaling network: receptor heterodimerization in development and cancer. The EMBO J. 2000,19: 3159-3167.
Richard C, William R. H., Michael A. L., Sarah E.H., William J.M. The Catalytic Activity of the ErbB-2 Receptor Tyrosine Kinase Is Essential for Embryonic Development. Molecular and Cellular Biology 2002, Feb: 1073-1078.
Robert R..J. The ErbB/HER receptor protein-tyrosine kinases and cancer. BBRC 2004, 319:1-11. Saxon M.L., Lee D.C. Mutagenesis reveals a role for epidermal growth factor receptor extracellular subdomain IV in ligand binding. J. Biol. Chem. 1999,274: 28356-28362.
Schneider J.W., Chang A.Y., Rocco T.P. Cardiotoxicity in signal transduction therapeutics: erbB2 antibodies and the heart. Semin. Oncol. 2001,28: S18-S26.
Semba K, Kamata N, Toyoshima K, Yamamoto T. A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erb-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc. Natl. Acad. Sci. 1985, 82: 6497-6501.
Shelly M, Mosesson Y, Citri A, Lavi S, Zwang Y, Melamed-Book N, Aroeti B, Yarden Y. Polar expression of
ErbB-2/HER2 in epithelia, Bimodal regulation by Lin-7. Dev. Cell 2003, 5: 475-486.
Shih C, Padhy L.C., Murray M., Weinberg R.A. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature 1981,290:261-264.
Uray I.P, Connelly J.H., Thoma'zy V, Shipley G.L., Vaughn V.K., Frazier H., Taegtmeyer H., Davies J.A. Left Ventricular Unloading Alters Receptor Tyrosine Kinase Expression in the Failing Human Heart. J. Heart Lung Transplant. 2002 July: 771-782.
Waterman H., Yarden Y. Molecular mechanisms underlying endocytosis and sorting of ErbB Wiley H.S.Trafficking of the ErbB receptors and its influence on signaling. Experimental Cell Research 2003, 284: 78-88.
Yarden Y. Biology of HER2 and its importance in breast cancer. Oncology 2001, 61: S1-S13.
Yarden Y., Sliwkowski M.X. Untangling the ErbB2 signaling network, Nat. Rev. Mol. Cell Biol. 2001b, 2: 127-136.
Hynes NE, Stem DF. The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim Biophys Acta. 1994, 1198:165-84
Ross J.S., Fletcher J.A. The HER2/neu oncogene: prognostic factor, predictive factor and target for therapy. Semin. Cancer Biol. 1999, 9: 125-138.
Piccart M, Lohrisch C., Leo A.D., Larsimont D. The Predictive Value of HER2 in Breast Cancer. Oncology 2001, 61: S73-S82.
Neve R. M., Lane H.A., Hynes N. E. The role of overexpressed HER2 in transformation. Annals of Oncology 2001, 12: S9-S13.
Pinkas-Kramarski R, Shelly M, Guarino BC, WangLM, Lyass L, Alroy I, Alimandi M, Kuo A, Moyer JD, Lavi S,
Eisenstein M, Ratzkin BJ, Seger R, Bacus SS, Pierce JH, Andrews GC, Yarden Y, Alamandi M: ErbB tyrosine kinases and the two neuregulin families constitute a ligand-receptor network. Mol. Cell Biol. 1998, 18:6090-6101.
Holbro T., Beerli R.R., Maurer F., Koziczak M., Barbas C.F., Hynes N. E. The ErbB2-ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. PNAS 2003, 100: 8933-8938.
Hsieh S.S., Malerczyk C., Aigner A., Czubayko F. ErbB-2 expression is rate-limiting for epidermal growth factor-mediated stimulation of ovarian cancer cell proliferation. Int. J. Cancer 2000, 86:644-651.
Neve, R. M., Lane, H.A., Hynes, N.E. The role of overexpressed HER2 in transformation, Annals of Oncology 2001, 12: S9-S13.
Timms JF, White SL, O'Hare M J, Waterfield MD. Effects of ErbB-2 overexpression on mitogenic signalling and cell cycle progression in human breast luminal epithelial cells, Oncogene. 2002, 21: 6573-6586.
Muraoka R. S, Anne E., Lenferink G., Law B., Hamilton E., Brantley D.M., Roebuck L.R, Arteaga C.L. ErbB2/Neu-Indueed, cyclin D1-dependent transformation is accelerated in p27-haploinsufficient mammary epithelial cells but impaired in p27-nuli cells. Mol. Cell. Biol. 2002, 22:2204-2219.
Jones S.M, Kazlauskas A., Growth factor-dependent signaling and cell cycle progression. FEBS Letters 2001, 490:110-116.
Zhou B. P., Liao Y, Xia W, Spohn B, Lee MH, Hung MC. Cytoplsmic localization of p21~(cip1/WAF1) by Akt-induced phosphorylation in HER2/neu-overexpressiong cells. Nat. Cell Biol. 2001, 3: 245-252.
Zhou B.P., Hu M.C., Miller S.A., Yu Z., Xia W., Lin S.Y., Hung M.C. Her-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway. J. Biol. Chem. 2000, 275:8027-8031.
Yang C., Ionescu-Tiba V., Bums K., Gadd M., Zukerberg L., Louis D.N., Sgroi D., Schmidt E.V. The role of the cyclin D1-dependent kinases in ErbB2-mediated breast cancer. Am. J. Pathol. 2004, 164:1031-1038.
Grossman S.R. p300/MDM2 complexs participate in MDM2-mediated p53 degradation. Mol. Cell 1998, 2: 405-415.
Tan M., Jing T., Lan K.H., Neal C.L. Phosphoraylation on Tyrosine-15 of p34Cdc2 by ErbB2 inhibits p34Cdc2activation and is involved in resistence to taxol-induced apoptosis. Mol. Cell 2002, 9: 993-1004.
Codony-Servat J., Albanell J., Lopez-Talavera J.C. et al. Cleavage of the HER2 ectodomain is a pervanadate-activable process that is inhibited by the tissue inhibitor of metalloproteases-1 in breast cancer cells. Cancer Res. 1999, 59: 1196-1201.
Huang H.S., Nagane M., Klingbeil C.K. et al. The enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers is mediated by threshold levels of constitutive tyrosine phosphorylation and unattenuated signaling. J. Biol. Chem.1997,272: 2927-2935.
Christianson T.A., Doherty J.K., Lin Y.J. et al. NH2-terminally truncated HER-2/neu protein: Relationship with shedding of the extracellular domain and with prognostic factors in breast cancer. Cancer Res 1998, 58: 5123-5129.
Worthylake R., Opresko L.K., Wiley H.S. ErbB2 amplification inhibits down-regulation and induces constitutive activation of both ErbB2 and epidermal growth factor receptors, J. Biol. Chem. 1999, 274: 8865-8874.
Hendriks B.S., Opresko L.K, Wiley H.S., Lauffenburger D. Coregulation of Epidermal Growth Factor Receptor/Human Epidermal Growth Factor Receptor 2 (HER2) Levels and Locations: Quantitative Analysis of HER2 Overexpression Effects, Cancer Res. 2003,63: 1130-1137.
Hendriks B.S., Opresko L.K., Wiley H.S., Lauffenburger D. Quantitative analysis of HER2-mediated effects on HER2 and epidermal growth factor receptor endocytosis: distribution of homo- and heterodimers depends on relative HER2 levels. J Biol. Chem. 2003, 278: 23343-23351.
Muthuswamy S.K., Gilman M., Brugge J.S. Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers. Mol. Cell. Biol. 1999,19: 6845-6857.
Verbeeka B.S., Adriaansen-Slota S.S., Vroomb T.M., Beckersc T., Rijksena G. Overexpression of EGFR and c-erbB2 causes enhanced cell migration in human breast cancer cells and NIH3T3 fibroblasts. FEBS Letters 1998, 425: 145-150.
Feldner J.C., Brandt B.H. Cancer cell motility—on the road from c-erbB-2 receptor steered signaling to actin reorganization. Exp. Cell. Res. 2002, 272: 93-108.
Dittmar T., Husemann A., Schewe Y., Nofer J.R., Niggemann B., Zanker K.S., Brandt B.H. Induction of cancer cell migration by epidermal growth factor is initiated by specific phosphorylation of tyrosine 1248 of c-erbB-2 receptor via EGFR. FASEB J. 2002, 16: 1823-1825.
Kathryn S.R. Spencer, Diana Graus-Porta, Jie Leng, Nancy E. Hynes, Richard L. Klemke. ErbB2 is necessary for induction of carcinoma cell invasion by ErbB family receptor tyrosine kinases. The Journal of Cell Biology, 2000; 148: 385-397.
Shepherd T.G., Kockeritz L., Szrajber M.R., Muller W.J., Hassell J.A. The pea3 subfamily ets genes are required for HER2/Neumediated mammary oncogenesis. Current Biology 2001,11: 1739-1748.
Nagae Y., Kameyama K., Yokoyama M, Naito Z., Yamada N., Maeda S., Asano G., Sugisaki Y., Tanaka S.. Expression of E-cadherin catenin and C-erbB-2 gene products in invasive ductal-type breast carcinomas. J. Nippon. Med.Sch. 2002,69: 165-171.
Wobus M, Rangwala R, Sheyn I, Hennigan R, Coila B, Lower EE, Yassin RS, Sherman LS. CD44 associates with EGFR and erbB2 in metastasizing mammary carcinoma cells. Appl Immunohistochem Mol. Morphol. 2002, 10: 34-39.
Jepson S, Komatsu M, Haq B, Arango ME, Huang D, Carraway CA, Carraway KL. Muc4/ sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Oncogene 2002,21: 7524-7532.
Adams G.P., Schier R., McCall A.M., Simmons H.H., Horak E.M., Alpaugh R.K., Marks J.D., Weiner L.M. High Affinity Restricts the Localization and Tumor Penetration of Single-Chain Fv Antibody Molecules, Cancer Res. 2001, 61: 4750—4755.
Arteaga C.L., Winnier A.R., Poirier M.C., Lopex-Larraza D.M., Shawver L.K., Hurd S.D., Stewart S.J. P185 c-erbB-2 signal enhances cisplatin-induced cytotoxicity in human breast carcinoma cells: association between an oncogenic receptor tyrosine kinase and drug-induced DNA repair. Cancer Res 1994, 54: 3758-3763.
Austin C.D., De Maziere A.M., Pisacane P.I., Van Dijk S.M., Eigenbrot C., Sliwkowski M.X., Klumperman J., Scheller R.H. Endocytosis and Sorting of ErbB2 and the Site of Action of Cancer Therapeutics Trastuzumab and Geldanarnycin. Mol Biol Cell 2004,15: 5268-82.
Bacus S.S., Stancovski I, Huberman E, Chin D, Hurwitz E, Mills G B, Ullrich A, Sela M, Yarden Y Tumor-inhibitory monoclonal antibodies to the HER-2/Neu receptor induce differentiation of human breast cancer cells. Cancer Res 1992, 52:2580.
Baselga J., Albanell J. (2001) Mechanism of action of anti-HER2 monoclonal antibodies. Ann. Oncol. S1:35-41.
Becerril B., Poul M.A., Marks J.D. Toward Selection of Internalizing Antibodies from Phage Libraries. Biochem. Biophys. Res. Commun. 1999, 255: 386-393.
Boyer C.M., Pusztai L., Wiener J.R., Xu F.J., Dean G.S, Bast B.S., O'Briant K.C., Greenwald M., Desombere K.A., Bast R.C. Relative cytotoxic activity of immunotoxins reactive with different epitopes on the extracellular domain of the c-erbb-2 (her-2/neu) gene product pl85. 1999 Int. J. Cancer. 82: 525-531.
Brian Leyland-Jones. Trastuzumab: hopes and realities. The Lancet 2002, 3: 137-144.
Cho H.S., Mason K., Ramyar K.X., Stanley A.M., Gabelli S.B., Denney D.W., Leahy D.J. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 2003,21: 756-760.
Cho H.S., Mason K., Ramyar K.X., Stanley A.M., Gabelli S.B., Denney D.W., Leahy D.J. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 2003,421:756-760.
Codony J., Albanell J., Arribas J., Baselga J.. Regulated shedding of the HER2 receptor ectodomain in human breast cancer cells. Proc. Am. Assoc. Cancer Res Annu. Meet 1999,40: 369-370.
Drebin J.A., Link V.C., Stern D.F., Weinberg RA, Greene MI. Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell 1985,41: 695- 706.
Drebin J.A., Link V.C.,Weinberg R.A,Greene MI: Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-e.ncoded tumor antigen. Proc Natl Acad Sci.USA. 1986,83: 9129 -9133.
Franklin M.C., Carey K.D., Vajdos F.F., Leahy D.J, Vos A.M, Sliwkowski M.X. Insights into ErbB2 signaling from the structure of the ErbB2-pertusumab complex. Cancer Cell 2004,5:317-327.
Franklin M.C., Carey K.D., Vajdos F.F., Leahy D.J, Vos A.M, Sliwkowski M.X. Insights into ErbB2 signaling from the structure of the ErbB2-pertusumab complex. Cancer Cell 2004,5:317-327.
Freebairn A.J.E., Last A.T.J., Illidge T.M. Trastuzumab: Designer Drug or Fashionable Fad? Clinical Oncology 2001, 13:427-433.
Harwerth I.M., Wels W., Schlegel J., Muller M., Hynes N.E.. Monoclonal antibodies directed to the erbB-2 receptor inhibit in vivo tumour cell growth. Br. J. Cancer 1993,68: 1140-1145.
Hommelgaard A.M., Lerdrup M., Van D.B. Association with membrane protrusions makes ErbB2 an internalization-resistant receptor. Mol Biol Cell 2004,15: 1557-67.
Hurwitz E., Stancovski I., Sela M., Yarden Y. Supperssion and promotion of tumor growth by monoclonal antibodies to ErbB-2 differentially correlate with cellular uptake. PNAS, 1995,92:3353-3357.
Kita Y., Tseng J., Horan T, Wen J, Philo J, Chang D, Ratzkin B, Pacifici R, Brankow D, Hu S, Luo Y, Wen D, Arakawa T, Nicolson M ErbB receptor activation, cell morphology changes, and apoptosis induced by anti-Her2 monoclonal antibodies. Biochem Biophys Res Comm 1996,226: 59
Klapper L.N., Vaisman N., Hurwitz E., Pinkaskramarski R., Yarden Y., Sela M. A subclass of tumor-inhibitory monoclonal antibodies to ErbB-2/Her2 blocks crosstalk with growth factor receptors. Oncogene 1997,14: 2099-2102.
Klapper L.N., Waterman H., Sela M., Yarden Y. Tumor-inhibitory antibodies to HER-2/ErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of HER-2. Cancer Res. 2000,60: 3384
Kumar R., Shepard H.M., Mendelsohn J. Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human mammary carcinoma cells. Mol. Cell. Biol. 1991, 11: 979-986.
Lane H.A., Motoyama A.B., Beuvink I., Hynes N.E. Modulation of p27/Cdk2 complex formation through 4D5-mediated inhibition of HER2 receptor signaling. Ann Oncol. 2001,12: S21-S22.
Le X.F., Amanda M.W., Wiener J., Wu J.Y., Mills G.B, and Bast R.C Jr. Anti-HER2 Antibody and Heregulin Suppress Growth of HER2-Overexpressing Human Breast Cancer Cells through Different Mechanisms. Clin. Cancer Res. 2000(a), 6:260-270.
Le X.F., Claret F.X., Lammayot A., Tian L., Deshpande D., Pushin R.L., Tari A.N., Bast R.C. The Role of Cyclin-dependent Kinase Inhibitor p27Kip1 in Anti-HER2 Antibody-induced G1 Cell Cycle Arrest and Tumor Growth Inhibition. J. Biol. Chem. 2003,278:23441-23450.
Le X.F., Ratna Vadlamudi, Amanda M., Bae D.S., Mills G.B., Kumar B., Bast R.C. Differential Signaling by an Anti-pl85HER2 Antibody and Heregulinl, Cancer Res. 2000(b), 60: 3522-3531.
Lee S., Yang W., Lan K.H., Sellappan S., Klos K., Hortobagyi G., Hung M.C , Yu D. Enhanced Sensitization to Taxol-induced Apoptosis by Herceptin Pretreatment in ErbB2- overexpressing Breast Cancer Cells. Cancer Res. 2002, 62:5703-5710.
Lewis Phillips GD, McMurtrey A.E., Schroeder K., Fendly B.M. Diverse activities of anti-HER2 monoclonal antibodies: from growth inhibition to induction of apoptosis. Proc Am Assoc Cancer Res. 1998, 39: 143-148.
Longva, K.E., Pedersen N.M., Haslekas, C, Stang, E., Madshus I.H. (2005) Herceptin-induced inhibition of ErbB2 signaling involves reduced phosphorlylation of Akt but not endocytic downr-egulation of ErbB2. Int. J. Cancer 116, 359-367.
Lorenzo C.D., Cozzolino R, Carpentieri A, Pucci P, Laccetti P, D'Alessio A. Biological properties of a human compact anti-ErbB2 antibody. Carcinogenesis 2005,11:1890-1895.
Lorenzo C.D., Palmer D.B., Piccoli R., Ritter M.A., D'Alession G. A new human antitumor immunoreagent specific for ErbB2. Clin. Cancer Res. 2002,8:1710-1719.
Molina, M. A. et al. Trastuzumab (Herceptin), a humanized anti-Her2 receptor monoclonal antibody inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells. Cancer Res. 2001, 61: 4744—4749.
Neve R.M., Nielsen U.B., Kirpotin D.B., Poul M.A., Marks J.D., Benz C.C. Biological Effects of Anti-ErbB2 Single Chain Antibodies Selected for Internalizing Function. Biochem. Biophys. Res. Commun. 2001,280: 274-279.
Pegram M., Hsu S., Lewis G. et al. Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene 1999,18:2241-2251.
Petit A.M., Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B, Kerbel R.S. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am.J.Pathol. 1997,151:1523
Pietras R.J., Fenly B.M., Chazin V.R., et al. Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells. Oncogene 1994,9: 1829-38
Pietras R.J., Pegram MD, Finn RS et al. Remission of human breast cancer xenografts on therapy with humanized monoclonal antibody to HER-2 receptor and DNA-reactive drugs. Oncogene 1998; 17: 2235-2249.
Pietras R.J., Poen JC, Gallardo D, Wongvipat PN, Lee HJ, Slamon DJ. Monoclonal antibody to HER-2/neu receptor modulated repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res 1999, 59: 1347-1354.
Poul, M.A., Becerril, B.,Nielsen, U.B., Morisson, P., Marks, J.D. Selection of Tumor-Specific Internalizing Human Antibodies from Phage Libraries, J. Mol. Biol. 2000,301: 1149-1161.
Sarup J.C., Johnson R.M. King K.L., Fendly B.M., Lapari M.T., Napier M.A., Ullrich A., Shepard H.M. Characterization of an anti-p185HER2 monoclonal antibody that stimulate receptor function and inhibits tumor cell growth. Growth Regul. 1: 72-77.
Sasaki S., Tsujisaki M, Jinnohara T, Ishida T, Sekiya M, Adachi M, Takahashi S, Hinoda Y, Imai K Human tumor growth suppression by apoptosis induced with anti-ErbB-2 chimeric monoclonal antibody. Jpn J Cancer Res 1998, 89:562
Shak S. Overview of the trastuzumab (Herceptin) anti-HER2 monoclonal antibody clinical program in HER2-overexpressing metastatic breast cancer. Herceptin Multinational Investigator Study Group. Semin Oncol 1999,26: 71-80.
Shawver L.K., Mann E., Elliger S.S., Dugger T.C., Arteaga C.L. Ligand-like effects induced by anti-c-erbB-2 antibodies do not correlate with and are not required for growth inhibition of human carcinoma cells. Cancer Res. 1994, 54:1367-1372.
Shawver L.K., Mann E., Elliger S.S., Dugger T.C., Arteaga C.L. Ligand-like effects induced by anti-c-erbB-2 antibodies do not correlate with and are not required for growth inhibition of human carcinoma cells. Cancer Res 1994, 54:1367
Spiridon C.I., Guinn S, Vitetta ES. A Comparison of the in Vitro and in Vivo Activities of IgG and F(ab)2 Fragments of a Mixture of Three Monoclonal Anti-Her-2 Antibodies. Clin. Cancer Res. 2004,10: 3542-3551.
Srinivas U., Tagliabue E., Campiglio M., Menard S., Colnaghi M.I., Antibody-induced activation of pl85HER2 in the human lung adenocarcinoma cell line Calu-3 requires bivalency, Cancer Immunol Immunother. 1993,36: 397-402.
Tagliabue E., Centis F., Campiglio M., Mastroianni A., Martignone S., Pellegrini R., Casalini P., Lanzi C, Menard S., Colnaghi M.I. Selection of monoclonal antibodies which induce internalization and phosphorylation of p185HER2 and growth inhibition of cells with HER2/NEU gene amplification. Int. I. Cancer 1991,47:933.
Tokuda Y./, Ohta M, Suzuki Y, Kubota M, Tajima T. Clinical development of trastuzumab in breast cancer. Breast Cancer. 2001, 8: 93-97.
Xu F., Lupu R., Rodriguez G.C., Whitaker R.S., Boente M.P., Berchuck A., Yu Y., Desombre K.A., Boyer C.M., Bast R.C. Antibody-induced growth inhibition is mediated through immunochemically and functionally distinct epitopes on the extracellular domain of the c-erbB-2 HER-2-neu gene product pl85. Int. J. Cancer 1993, 53: 401-406.
Xu F.J., Boyer CM, Bae DS, Wu S, Greenwald M, O'Briant K, Yu YH, Mills GB, Bast RC Jr. The tyrosine kinase activity of the C-erbB-2 gene product (p185) is required for growth inhibition by anti-p185 antibodies but not for the cytotoxicity of an anti-p185-ricin-A chain immunotoxin. Int. J. Cancer 1994,59:242.
Yakes F.M., Chinratanalab W. , Ritter C.A., King W., Seelig S., Arteaga C.L. Herceptin- induced Inhibition of Phosphatidylinositol-3 Kinase and Akt Is Required for Antibody-mediated Effects on p27, Cyclin D1, and Antitumor Action, Cancer Res. 2002,62: 4132-4141.
Ye D., Mendelsohn J., Fan Z. Augmentation of a humanized anti-HER2 mAb 4D5 induced growth inhibition by a human-mouse chimeric anti-EGF receptor mAb C225. Oncogene 1999,18: 731-738.
Yip L.Y., Ward R.L. (2002) Anti-ErbB2 monoclonal antibodies and ErbB2-directed vaccines. Cancer. Immunol. Immunother. 50: 569-587.
Yip Y.M., Novetny J., Edwards M., Ward R.L. Structural analysis of the ErbB2 receptor using monoclonal antibodies: Implications for receptor signaling. Int. J. Cancer 2003,104: 303-309.
Yip Y.M., Smith G., Koch J., Dubel S., Ward R. Identification of epitope regions recognized by tumor inhibitory and stimulatory anti-ErbB2 monoclonal antibodies: Implications for vaccine design. J. Immunol. 2001,166: 5271-5278.
Zhang H., Wang Q., Montone K.T., Peavey J.E., Drebin J.A., Greene M.I., Murali R. Shared Antigenic Epitopes and Pathobiological Functions of Anti-pl85her2/neu Monoclonal Antibodies. Exp. Mol. Pathol. 1999,67: 15-25.
Park BW, Zhang HT, Wu C, Berezov A, Zhang X, Dua R, et al.: Rationally designed antiher2/neu peptide mimetic disables pl85her2/neu tyrosine kinases in vitro and in vivo. Nat Biotechnol. 2000,18: 194-198.
Berezov A, Zhang HT.Greene MI, Murali R: Disabling erbb receptors with rationally designed exocyclic mimetics of antibodies: Structurefunction analysis. J Med Chem 2001,44: 2565-2574.
Azemar M., Schmidt M, Arlt F, Kennel P, Brandt B, Papadimitriou A, Groner B, Wels W. Recombinant antibody toxins specific for ErbB2 and EGF receptor inhibit the in vitro growth of human head and neck cancer cells and cause rapid tumor regression in vivo. Int J Cancer 2000; 86:269-75.
Biburger M., Weth R. Wels W.S. A Novel Bispecific Tetravalent Antibody Fusion Protein to Target Costimulatory Activity for T-cell Activation to Tumor Cells Overexpressing ErbB2/HER2. J. Mol. Biol. 2005, 346:1299-1311.
Bird R. E., Hardman KD, Jacobson JW, Johnson S, Kaufman BM, Lee SM, Lee T, Pope SH, Riordan GS, Whitlow M. Single-chain antigen-binding proteins. Science 1988, 242: 423-426.
Can Y., Suresh M. R. Bispecific antibodies as novel bioconjugates. Bioconjug. Chem. 1998, 9: 635-644.
Carter P., Presta L., Gorman C.M., Ridgway J.B., Henner D., Wong W.L., Rowland A.M., Kotts C., Carver M.E.,Shepard H.M.. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci U S A 1992; 89:,1285-4289.
Chowdhury P. S. Engineering hot spots for affinity enhancement of antibodies. Methods Mol. Biol. 2003, 207: 179-196.
Dail'Acqua W. F., Damschroder M. M., Zhang J., Woods R. M., Widjaja L. Antibody humanization by framework shuffling. Methods. 2005, 36: 43-60.
De J. J., Brissinck J, Heirman C, Demanet C, Leo O, Moser M, Thielemans K. Production and characterization of bispecific single-chain antibody fragments. Mol Immunol 1995; 32:1405-1412.
Gerstmayer B., Altenschmidt U, Hoffmann M, Wels W. Costimulation of T cell proliferation by a chimeric B7-2 antibody fusion protein specifically targeted to cells expressing the erbB2 proto-oncogene. J. Immunol. 1997, 158: 4584-4590.
Hanes J, Jermutus L, Weber-Bornhauser S, Bosshard HR, Pluckthun A. Ribosome display efficiently selects and evolves high-affinity antibodies in vitro from immune libraries. Proc Natl Acad Sci U S A 1998,95: 14130-14135.
Hanes J, Pluckthun A. In vitro selection and evolution of functional proteins by using ribosome display. Proc. Natl. Acad. Sci. 1997,94: 4937-4942.
Helguera G., Morrison S. L., Penichet M. L. Antibody-Cytokine Fusion Proteins: Harnessing the Combined Power of Cytokines and Antibodies for Cancer Therapy. Clin. Immun. 2002,105:233-246.
Ho, M., Kreitman, R. J., Onda, M., and Pastan, I. (2005) In vitro antibody evolution targeting germline hot spots to increase activity of an anti-CD22 immunotoxin. J. Biol. Chem. 280, 607-617.
Hu S, Shively L, Raubitschek A, Sherman M, Williams LE, Wong JY, Shively JE, Wu AM. Minibody: A novel engineered anti-carcinoembryonic antigen antibody fragment (single chain Fv-CH3) which exhibits rapid, high-level targeting of xenografts. Cancer Res 1996; 56:3055-3061.
Huls, G. A., Heijnen, I. A., Cuomo, M. E., Koningsberger, J. C, Wiegman, L., et al. (1999) A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments. Nat. Biotechnol. 17,276-281.
Hwang, W. Y. K., Almagro, J. C, Buss, T. N., Tan, P., and Foote, J. (2005) Use of human germline genes in a CDR homologybased approach to antibody humanization. Methods 36,35-42.
Irving R.A., Coia G., Roberts A., Nuttall S.D., Hudson P.J. Ribosome display and affinity maturation: from antibodies to single V-domains and steps towards cancer therapeutics. J. Immunol. Methods 2001,248: 31-45. Jia L. et al. Specific Tumoricidal Activity of a Secreted Proapoptotic Protein Consisting of HER2 Antibody and Constitutively Active Caspase-3. Cancer Res. 2003,63: 3257-3262.
Jones, P.T., Dear, P.H., Foote, J., Neuberger, M.S., and Winter, G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 1996, 321: 522-525.
Kashmiri, S. V., De Pascalis, R., Gonzales, N. R., and Schlom, J. SDR grafting-a new approach to antibody humanization. Methods. 2005,36: 25-34.
Knappik A., Ge, L., Honegger, A., Pack, P., Fischer, M., et al. (2000) Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs with randomized trinucleotides. J. Mol. Biol. 296, 57-86.
Le GF, Kipriyanov SM, Moldenhauer G, Little M. Di-, tri- and tetrameric single chain Fv antibody fragments against human CD19: effect of valency on cell binding. FEBS Lett 1999; 453:164-168.
Lorenzo C.D., Nigro A., Piccoli R., D'Alessio G. A new RNase-based immunoconjugate selectively cytotoxic for ErbB2-overexpressing cells. FEBS Letters 516 (2002) 208-212.
Marshall KW, Marks JD. Engineering and characterization of a novel fusion protein incorporating B7.2 and an anti-ErbB-2 single-chain antibody fragment for the activation of Jurkat T cells. J Immunother 2001; 24:27-36.
Maurer-Gebhard M, Schmidt M, Azemar M, Altenschmidt U, Stocklin E, Wels W, Groner B. Systemic treatment with a recombinant erbB-2 receptor-specific tumor toxin efficiently reduces pulmonary metastases in mice injected with genetically modified carcinoma cells. Cancer Res 1998; 58:2661-6.
McCall AM, Adams GP, Amoroso AR, Nielsen UB, Zhang L, Horak E, Simmons H, Schier R, Marks JD, Weiner LM. Isolation and characterization of an anti-CD16 single-chain Fv fragment and construction of an anti-HER2/neu/anti-CD16 bispecific scFv that triggers CD16-dependent tumor cytolysis. Mol. Immunol. 1999, 3:433-445.
Morrison, S. L., Johnson, M. J., Herzenberg, L. A., and Oi, V. T. Chimeric human antibody molecules; mouse antigenbinding antigen binding domains with human constant region domains. Proc. Natl Acad. Sci. USA 1984, 21: 6851-6855.
Reiter Y, Brinkmann U, Webber KO, Jung SH, Lee B, Pastan I. Engineering interchain disulfide bonds into conserved framework regions of Fv fragments: improved biochemical characteristics of recombinant immunotoxins containing disulfide-stabilized Fv. Protein Eng 1994; 7:697-704.
Rohrbach F, Gerstmayer B, Biburger M, Wels W. Construction and characterization of bispecific costimulatory molecules containing a minimized CD86 (B7-2) domain and single-chain antibody fragments for tumor targeting. Clin Cancer Res 2000; 6:4314-22.
Schier R, Bye J., Apell G., McCall A. Adams G.P., Malmqvist M., Weiner L.M., Marks J.D. Isolation of High-affinity Monomeric Human Anti-c-erbB-2 Single chain Fv Using Affinity-driven Selection. J. Mol. Biol. 1996,255: 28-43.
Schier, R., McCall, A., Adams, G. P., Marshall, K. W., Merritt, H., Marks J.D. Isolation of picomolar affinity anti-c-erbB-2 single-chain Fv by molecular evolution of the complementarity determining regions in the center of the antibody binding site. J. Mol. Biol. 1996,263: 551-567.
Schmidt M, McWatters A, White RA, Groner B, Wels W, Fan Z, Bast RC Jr. Synergistic interaction between an anti-p185HER-2 pseudomonas exotoxin fusion protein [scFv(FRP5)-ETA] and ionizing radiation for inhibiting growth of ovarian cancer cells that overexpress HER-2. Gynecol Oncol 2001; 80:145-55.
Skerra A, Pluckthun A. Assembly of a functional immunoglobulin Fv fragment in Escherichia coli. Science 1988; 240:1038-1041.
Tsurushita, N., Hinton, P. R., and Kumar, S. (2005) Design of humanized antibodies: from anti-Tac to Zenapax. Methods 36: 69-83.
Vaughan, T. J., Williams, A. J., Pritchard, K., Osbourn, J. K., Pope, A. R., et al. (1996) Human antibodies with subnanomolar affinities isolated from a large non-immunized phage display library. Nat. Biotechnol. 14,309-314.
Wang L, Liu B, Schmidt M, Lu Y, Wels W, Fan Z. Antitumor effect of an HER2-specific antibody-toxin fusion protein on human prostate cancer cells. Prostate 2001; 47:21-8.
Andersen D. C. Krummen L. Recombinant protein expression for therapeutic applications. Curr. Opin. Biotechnol. 2002, 13: 117-123.
Andrade E. V., Albuquerque F.C.., Moraes L.M., Brigido M.M., Santos-Silva M.A.. Single-chain Fv with Fc Fragment of the Human IgGl Tag: Construction, Pichia pastoris Expression and Antigen Binding Characterization. J. Bioehem. 2000, 128:891-895.
Brierley R.A., Davis R.G., HoItz C.G. Production of insulin-like growth factor-I in methylotrophic yeast cells. 1994. US Patent No. 5,324,639.
Brocca S., Schimidt-dannert C, Lotti M. Alberghina L, Schmid R.D. Design, total synthesis, and functional over expression of the Candida rugosa lip1 gene coding for a major industrial lipase, Protein Science, 1998, 7: 1415-1422
Byrne M.P., Titball R.W., Holley J., Smith L.A. Fermentation, Purification, and Efficacy of a Recombinant Vaccine Candidate against Botulinum Neurotoxin Type F from Pichia pastoris. Protein Expres. Purif. 2000, 18: 327-337.
Caldas C, Coelho V., Rigden D.J., Neschich G., Moro A.M., Brigido M.M. Design and synthesis of germline-based hemi-humanized single-chain Fv against the CD18 surface antigen. Protein Eng. 2000,13: 353-360.
Cereghino G.P.L., Cereghino J.L., Ilgen C, Cregg J. Production of recombinant proteins in fermenter cultures of the yeast Pichia pastoris. Curr. Opin. Biotechnol. 2002,13: 329-332.
Cereghino J.L., Cregg J.M.. Heterloguos protein expression in the methylotrophic yeast Pichia pastoris. FEMS Microbiol. Rev. 2000, 24: 45-66.
Chang H.K., Oh Y., Lee T.H. Codon optimization for high-level expression of human erythropoietin (EPO) in mammalian cells. Gene, 1997:293-301.
Cho GH, Lee DH, Min WK, Cho YJ, Kweon DH, Son DH, Park K, Seoa JH. Cloning, expression, and characterization of single-chain variable fragment antibody against mycotoxin deoxynivalenol in recombinant Escherichia coli. Protein Expres. Purif. 2004, 35: 84-92.
Clare J.J., Rayment F.B., Ballantyne S.P., Sreerkrishna K., Romanos M.A. High-level expression of tetanus toxin fragment C in Pichia pastoris strains containing multiple tandem integrations of the gene. BioTechnology 1991, 9: 455-460.
Coghlan A., Wolfe K.H . Relationship of codon bias to mRNA concentration and protein length in Saccharomyces cerevisiae. Yeast 2002,16:1131-1145.
Cupit, P.M. Whyte J.A., Porter A.J., Browne M.J., Holmes S.D., Harris W.J. Cunningham C. Clone and expression of single chain antibody fragments in Escherichia coli and Pichia pastoris. Letters Appl. Microbiol. 1999,29:273-277;
Daly R., Hearn M.T.W. Expression of heterologous proteins in Pichia pastoris: a useful experimental tool in protein engineering and production J. Mol. Recognit. 2005,18:119-138.
Damasceno L.M., Pla I., Chang H.J., Cohen L., Ritter G., Old L.J., Battc C.A., An optimized fermentation process for high-level production of a single-chain Fv antibody fragment in Pichia pastori. Protein Expres. Purif. 2004, 37: 18-26.
Delroisse J.M., Dannau M., Gilsoul J.J., Mejdoub J.E., Destain J., Portetelle D., Thonart P., Haubruge E., Vandenbol M., Expression of a synthetic gene encoding a Tribolium castaneum carboxylesterase in Pichia pastoris. Protein Expres. Purif. 2002, 42:286-294.
Eldin P., Pauza M.E., Hieda Y., Lin G., Murtaugh M.P., Pentel P.R., Pennell C.A. High-level secretion of two antibody single chain Fv fragments by Pichia pastoris. J Immunol. Methods 1997,201:67-75.
Eldin P., Pauza M.E., Hieda Y., Lin G., Murtaugh M.P., Pentel P.R., Pennell C.A. High-level secretion of two antibody single chain Fv fragments by Pichia pastoris. J. Immunol. Methods, 1997,201: 67-75.
Emberson L.M., Trivett A.J., Blower P.J., Nicholls P.J. Expression of an anti-CD33 single-chain antibody by Pichia pastoris. J. Immunol. Methods 2005, 305: 135-151.
Fischer R.. Drossard J., Emans N., Commandeur U. Hellwig S. Towards molecular farming in the future: Pichia pastoris-based production of singe-chain antibody fragments. Biotech. Appl. Biochem. 1999, 30: 117-120.
Freyre F.M., Vazquez J.E., Ayala M., Canaan-Haden L., Bell H., Rodriguez I., Gonzalez A., Cintado A., Gavilondo J.V. Very high expression of an anti-carinoembryonic antigen single chain Fv antibody fragment in the yeast Pichia pastoris. J. Biotechnol. 2000, 76: 157-163.
Goe A., Beresford G.W., Colcher D., Pavlinkova G.,Booth JM.B., Baranowska-Kortylewicz J., Batra S.K. Divalent Forms of CC49 Single-chain Antibody Constructs in Pichia pastoris: Expression, Purification, and Characterization. J. Biochem. 2000,127: 829-836.
Goel A., Colcher D., Baranowska-Kortylewicz J., Augustine S., Booth B.J., Pavlinkova G., Batra S.K. Genetically engineered tetravalent single-chian Fv of the pancarcinoma monoclonal antibody CC49: Improved biodistribution and potential for therapeutic application. Cancer Res. 2000, 60:6964-6971.
Gurkan C, Symeonides S.N, Ellar DJ. High-level production in Pichia pastoris of an anti-pl85HER-2 single-chain antibody fragment using an alternative secretion expression vector. Biotechnol Appl Biochem. 2004, 39: 115-122.
Hellwig S., Emde F., Raven N.P., Henke M., van Der Logt P., Fischer R. Analysis of single chain antibody production in pichia pastoris using on-line methanol control in fed-batch and mixed-feed fermentations. Biotechnol. Bioengineer. 2001,74: 344-352.
Hoekema A., Kastelein R.A., Vasser M., Boer H.A. Codon replacement in the PGK1 gene of Saccharomyces cerevisiae: Experimental approach to study the role of biased codon usage in gene expression. Mol. Cell. Biol. 1987, 7: 2914-2924.
Hohenblum H., Gasser B., Maurer M., Borth N., Mattanovich D. Effects of gene dosage, promoters, and substrates on unfolded protein stress of recombinant Pichia pastoris. Biotechnol. Bioeng. 2004,85: 367-375.
Hong F. Fermentation Strategies for Improved Heterlogous Expression of Laccase in Pichia pastoris, Biotechnol. Bioeng. 2002, 79(4): 438-449;
Jurado P., Ritz D., Beckwith J., Lorenzo V. Ferna'ndez L.A. Production of Functional Single-Chain Fv Antibodies in the Cytoplasm of Escherichia coli. J. Mol. Biol. 2002,320:1-10.
Kobayashi K., Kuwae S., Ohya T., et al. Addition of oleic acid increases expression of recombinant human serum albumin by the AOX2 promoter in Pichia pastoris. J Biosci Bioeng 2000,89:479-484.
Kocken C.H., Withers-Martinez C, Dubbeld M.A., Wei A., Hackett F., Valderrama A., Blackman M.J., Thomas AW. High-Level Expression of the Malaria Blood-Stage Vaccine Candidate Plasmodium falciparum Apical Membrane Antigen 1 and Induction of Antibodies That Inhibit Erythrocyte Invasion. Infect. Immunity 2002,70: 4471-4476.
Koganesawa N., Aizava T., Shimojo H., et al. Expression and purification of a small cytokine growth-blocking peptide from armyworm Pseudaletia separata by an optimized fermentation method using the methylotrophic yeast Pichia pastoris. Protein Express. Purif. 2002.25: 416-425.
Lange S., Schmitt J., Schmid R.D. High-yield expression of the recombinant, atrazine-specific Fab fragment K411B by the methylotrophic yeast Pichia pastoris, J. Immunol. Methods 2001,255: 103-114.
Li Z., Xiong F., Lin Q, et al. Low temperature increases the yield of biologically active herring antifreeze protein in Pichia pastoris. Protein Expres. Purif. 2001,21:438-445.
Liu J., Wei D., Qian F., Zhou F., Wang J., Ma Y. Han Z. pPIC9-Fc: A Vector System for the Production of Single-Chain Fv-Fc Fusions in Pichia pastoris as Detection Reagents In Vitro J. Biochem. 2003,134: 911-917.
Luo D., Geng M., Noujaim A.A., Madiyalakan R. An engineered bivalent single-chain antibody fragment that increases antigen binding activity. J. Biochem. 1996,121: 831-834.
Luo D., Mah N., Wishart D., Zhang Y., Jacobs F., Martin L. Construction and expression of bi-functional proteins of single-chain Fv with effector domains. J Biochem. 1996,120: 229-232.
Macauley-Patrick S., Fazenda M.L., McNeil B., Harvey L.M. Heterologous protein production using the Pichia pastoris expression system. Yeast. 2005,22: 249-270.
Mahiouz D.L., Aichinger G., Haskard D.O. George A.J.T. Expression of recombinant anti-E-selectin singlechain Fvantibody fragment in stably transfected insect cell lines. J Immunol Methods 1998,212: 149-160.
Marshall K.W., Marks J.D. Engineering and characterization of a novel fusion protein incorporating B7.2 and an anti-ErbB-2 single-chain antibody fragment for the activation of Jurkat T cells. J Immunother. 2001, 24: 27-36.
Marty C, Scheidegger P, Ballmer-Hofer K, Klemenz R, Schwendener RA. Production of Functionalized Single-Chain Fv Antibody Fragments Binding to the ED-B Domain of the B-isoform of Fibronection in Pichia pastoris. Protein Expres Purif. 2001,21: 156-164.
Menendez J., Hernandez L., Banguela A., Pais J. Functional production and secretion of the Gluconoacetobacter diazatrophicus fructose-releasing exo-levanase (LsdB) in Pichia pastoris. Enz. Microb. Technol. 2004.34: 446-452.
Ning D., Xiang J., Wang X., Chen., Zhang Q., Su K., Rao G., Ren X., Long Q.,Yu Z. Expression, Purification, and Characterization of Humanized Anti-HBs Fab Fragment. J. Biochem. 2004,134: 813-817.
Ogunjimi A.A., Chandler J.M., Gooding C.M., Recinos R. Choudary P.V. High-level secretory expression of immunologically active intact antibody from the yeast Pichia pastoris. Biotechnol. Letters 1999,21: 561-567.
Outchkourov N.S., Stiekema W.J., Jongsma M.A. Optimization of the Expression of Equistatin in Pichia pastoris. Protein Expres. Purif. 2002,24: 18-24.
Percudani R, Pavesi A, Ottonello S (1997) Transfer RNA gene redundancy and translation selection in Saccharomyces cerevisiae. J Mol Biol 268:322-330
Powers D.B., Amersdorfer P., Poul M.A., Nielsen U.K., Shalaby M.R., Adams G.P., Weiner L.M., Marks J.D. Expression of single-chian Fv-Fc fusions in Pichia pastoris. J. Immunol. Methods 2001,251: 123-135.
Rahbarizadeh F., Rasaee M.J. Forouzandeh M., Allameh A.A. Over expression of anti-MUCl single-domain antibody fragments in the yeast Pichia pastoris Mol. Immunol. 2006,43:426-435.
Raju T.S., Briggs J., Borge S.M., Jones A.J.S. Species-specific variation in glycosylation of IgG: evidence for the species-specific sialylation and branch-specific galactosylation and importance for engineering recombinant glycoprotein therapeutics. Glycobiol. 2000,10:477-486.
Richard L.B. Milek, Hendrik G. Stunnenberg, Ruud N.H. Konings. Assembly and expression of a synthetic gene encoding the antigen Pfs48/45 of the human malaria parasite Plasmodium falciparum in yeast. Vaccine 2000, 18: 1402-1411.
Ridder R., Schmitz R., Legay F., Gram H. Generation of rabbit monoclonal antibody fragments from a combinatorial phage display library and their production in the yeast Pichia pastoris. Biotechnology 1995,13: 255-260.
Ridder R.,et al, Generation of rabbit monoclonal antibody fragments from a combinational phage display library and their production in the yeast. Biotechnol. 1995,13:255-260.
Sarramegna V., Demange P., Milon A., Talmont F. Optimizing Functional versus Total Expression of the Human u-Opioid Receptor in Pichia pastoris, Protein Expres. Purif. 2002,24:212-220.
Sharp P.M, Tuohy T., Mosurski K.R. Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucl. Acids Ras. 1986, 14.
Sharp P.M., Cowe E. (1991) Synonymous codon usage in Saccharomyces cerevisiae. Yeast 7:657-678
Sharp P.M., Li W.H. The codon adaptation index - a measure of directional synonymous codon usage bias, and its potential applications. Nucl. Acids Res. 1987,15:1281-1295.
Sharp P.M., Stenico M., Peden J.F., Lloyd A.T. Codon usage: mutational bias, translational selection, or both? Biochemistry Society Trans. 1993,21: 835-846.
Shi X., Karkut T., Chamankhah M., et al. Optimal conditions for the expression of a single-chain antibody (scFv) gene in Pichia pastoris. Protein Expres. Purif. 2003, 28:321-330.
Shinkawa, T., Nakamura, K., Yamane, N., Shoji-Hosaka, E., Kanda, Y. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgGl complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J. Biol, Chem. 2003, 278: 3466-3473.
Sinclair G. Synonymous codon usage bias and the expression of human glucocerebrosidase in the methylotrophic yeast Pichia pastoris. Protein Expres. Purif. 2002, 26: 96-105.
Sinclair G., Choy F. Synonymous codon usage bias and the expression of human glucocerebrosidase in the methylotrophic yeast Pichia pastoris. Protein Expres. Purif. 2002, 26: 96-105.
Sreekrishna K. Strategies for optimizing protein expression expression and secretion in the methylotrophic yeast Pichia pastoris, in "Industrial Microorganisms: Basic and Applied Molecular Genetics". Am. Soc. Microbiol., Washington, DC. 1993: 19-126.
Sreekrishna K., Brankamp R. G., Kropp K. E., Blankenship D. T., Tsay J.T., Smith P.L., Wierschke J.D., Subramaniam A., Birkenberger L.A. Strategies for optimal synthesis and secretion of heterloguos proteins in the methylotrophic yeast Pichia pastoris. Gene 1997, 190: 55-62.
Vassileva A., Chugh D.A., Swaminathan S., Khanna N. Effect of Copy Number on the Expression Levels of Hepatitis B Surface Antigen in the Methylotrophic Yeast Pichia pastoris. Protein Expres. Purif. 2001, 21: 71-80.
Venturi M., Seifert C., Hunte C., High Level Production of Functional Antibody Fab Fragments in an Oxidizing Bacterial Cytoplasm. J. Mol. Biol. 2002, 315: 1-8.
Wang Y., Wang K., Jette D.C., Wishart D.S. Production of an anti-prostate-specific antigen single-chain antibody fragment form Pichia pastoris. Protein Expres. Purif. 2001, 23: 419-425.
Wolff A.M., Hansen O.C., Poulsen U., Madrid S., Stougaard P. Optimization of the Production of Chondrus crispus Hexose Oxidase in Pichia pastoris. Protein Expres. Purif. 2001, 22: 189-199.
Woo J. H., Liu Y.Y., Mathias A, Stavrou S., Wang Z., Thompson J., Neville D.M. Gene optimization is necessary to express a bivalent anti-human anti-T cell immunotoxin in Pichia pastoris, Protein Expres. Purif. 2002, 25: 270-282.
Woo J. H., Liu Y. Y., Stavrou S., Neville D.M., Increasing Secretion of a Bivalent Anti-T-Cell Immunotoxin by Pichia pastoris. Appl. Environ. Micorbiol. 2004, 70: 3370—3376.
Xia X. How Optimized Is the Translational Machinery in Escherichia coli, Salmonella typhimurium and Saccharomyces cerevisiae? Genetics 149: 37-44 (May, 1998)
Xia X. Maximizing Transcription Efficiency Causes Codon Usage Bias. Genetics 1996, 144: 1309-1320.
Zhang Z, Zhi-Hua Li, Fei Wang, Min Fang, Chang-Cheng Yin, Zhi-Yong Zhou, Qing Lin, and Hua-Liang Huang. Overexpression of DsbC and DsbG markedly improves soluble and functional expression of single-chain Fv antibodies in Escherichia coli. Protein Expres. Purif. 2002, 26: 218-228.
贝锦龙等．人工合成黑曲霉基因NRRL3135菌株植酸酶基因在毕赤酵母系统中的高效表达．生物工程学报，2001，17：254-258．
黄秉仁等．人工合成表皮生长因子基因在甲基营养型酵母中的高效表达．中国生化与分子生物学报．1998，14：512-517．
姚斌，张春义，王建华．高效表达具有生物学活性植酸酶．中国科学C辑．1998，14．
赵翔，霍克克，李育阳．毕赤酵母密码子用法分析．生物工程学报．2000，16．
Atoda H., Ishikawa M., Mizuno H., Morita T., 1998. Coagulation Factor X-Binding Protein from Deinagkistrodon acutus venom is a Gla domain-binding protein. Biochemistry 37, 17361-17370.
Atoda H., Kaneko H., Mizuno H., Morita T. Calcium-binding analysis and molecular modeling reveal echis coagulation factor IX/factor X-binding protein has the Ca-binding properties and Ca ion-independent folding of other C-type lectin-like proteins. FEBS Letters 2002, 531: 229-234.
Atoda, H., Ishikawa, M., Yoshihara, E., Sekiya, F., Morita, T., 1995. Blood coagulation factor Ⅸ-binding protein from the venom of Trimeresurus flavoviridis: purification and characterization. J. Biochem. 118, 965-973.
Drickamer, K. C-type lectin-like domains. Curr. Opin. Struet. Biol. 1999, 9: 585-590.
Li W. F., Chen L., Li X.M., Liu J. A C-type lectin-like protein from Agkistrodon acutus venom binds to both platelet glycoprotein Ib and coagulation factor Ⅸ/factor. Biochem. Biophys. Res. Commun. 2005, 332: 904-912.
Lu Q., Navdaev A., Clemetson J.M., Clemetson K.J. Snake venom C-type lectins interacting with platelet receptors. Structure-function relationships and effects on haemostasis. Toxicon 2005,ⅩⅩ:1-10.
Mizuno H., Fujimoto Z., Atoda H., Morita T. Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X. Proc. Nat. Acad. Sci. 2001, 98: 7230-7234.
Morita.T. Structures and functions of snake venom CLPs (C-type iectin-like proteins) with anticoagulant-, procoagulant-, and platelet-modulating activities. Toxicon 2005, 45: 1099-1114.
Myers D. D., Wakefield T.W. Inflammation-Dependent Thrombosis. Front. Bioscience 2005, 10: 2750-2757.
Ogawaa T., Chijiwab T., Uedab K.O., Ohno M. Molecular diversity and accelerated evolution of C-type lectin-like proteins from snake venom. Toxicon 2005, 45: 1-14.
Paaventhan P., Kong C, Joseph J.S., Chung M.C., Kolatkar P.R. Structure of rhodocetin reveals noncovalently bound heterodimer interface. Protein Science 2005,4: 169-175.
Tani A., Ogawa T., Nose T., Nikandrow N.N., Deshimaru M., Chijiwa T., Chang C.C., Fukumaki Y., Ohno M., 2002. Characterization, primary structure and molecular evolution of anticoagulant protein from Agistrodon actus venom. Toxicon 40, 803-813.
Xu X.L., Liu Q.L., 2001. Binding of anticoagulation factor II from the venom of Agkistrodon acutus with activated coagulation factor X. Toxicon. 39: 1359-1365.
Xu X.L., Liu Q.L., Xie Y.Sh, Wu Sh.D., 2000. Purification and characterization of anticoagulation factors from the venom of Agkistrodon acutus. Toxicon 38,1517-1528.
Yu H., Xiang K., Wang Y., Liu J., 2003. Cloning and sequencing of eleven cDNAs of C-type lectin-like protein subunits from Agkistrodon Acutus. Chinese Journal of Biochemistry and Molecular Biology 19(1), 64-70.
Beatty J. D., Beatty B.G., Vlahos W.G. Measurement of monoclonal antibody affinity by non-competitive enzyme immunoassay. J. Immunol. Methods 1987, 26: 173-179.
Brocca S., Schmidt-Dannert C., Lotti M., Alberghinaand L., Schmid R.D. Design, total synthesis, functional overexpression of the Candida rugosa lip 1 gene coding for a major industrial lipase. Protein Sci. 1998, 7: 1415-1422.
Chen L. S., Liu A. P., Liu. J. Construction, expression and characterization of the engineered antibody against tumor surface antigen P185~(c-erbb-2). Cell Res. 2003, 13: 35-48.
Daly R., Hearn M. T. W. Expression of heterologous proteins in Pichia pastoris: a useful experimental tool in protein engineering and production. J. Mol. Recognit. 2005, 18:119-138.
Herrick D., Parker R., Jacobson A. Identification and comparison of stable and unstable mRNAs in Saccharomyces cerevisiae. Mol. Cell. Biol. 1990, 10: 2269-2284.
Hoekema A., Kastelein R. A., Vasser M., Boer H.A. Codon replacement in the PGK1 gene of Saccharomyces cerevisiae: experimental approach to study the role of biased codon usage in gene expression. Mol. Cell. Biol. 1987, 7: 2914-2924.
Hohenblum H., Gasser B., Maurer M., Borth N., Mattanovich D. Effects of Gene Dosage, Promoters, and Substrates on Unfolded Protein Stress of Recombinant Pichiapastoris. Biotechnol. Bioeng. 2004, 85: 367-375.
Kauffman K. J., Pridgen E. M., Doyle F. J., Dhurjati P. S., Robinson A.S. Decreased protein expression and intermittent recoveries in BiP levels result from cellular stress during heterologous protein expression in Saccharorayces cerevisiae. Biotechnol. Prog. 2002, 18: 942-950.
Kim C. H., Younghoon O., Lee T. H. Codon optimization for high-level expression of human erythropoietin (EPO) in mammalian cells. Gene 1997, 199: 293-301.
Li P., Li Y., Wang C., Liu J. Investigation on anti-cancer activities of anti-P185 monoclonal antibodies in vitro. Chinese J. Immunol. 2002, 18: 33-35.
Li, P., Li, Y., Wang, C., Liu, J. (2003) Characterization and utilization of twon novel anti-ErbB2 monoelonal antibodies in detection of soluble ErbB-2 for breast cancer prognosis.
Liu S. H., W. I. Choua, C.C. Sheub, Changa M.D. Improved secretory production of glucoamylase in Pichia pastoris by combination of genetic manipulations. Biochem. Biophys. Res. Commun. 2005, 326:817-824.
Oliveira C.C., Heuvel J.J., McCarthy J.E.G. Inhibition of translational initiation in Saccharomyces cerevisiae by secondary structure: the roles of the stability and position of stem-loops in the mRNA leader. Mol. Microbiol. 1993, 9: 521-532.
Outchkourov N. S., Stiekema W.J., Jongsma M. A. Optimization of the Expression of Equistatin in Pichia pastoris, Protein Expres. Purif. 2002, 24: 18-24.
Prodromou C., Pearl L. H. Recursive PCR: a novel technique for total gene synthesis. Protein Eng. 1992, 8: 827-829.
Powers D. B., Amersdorfer P., Poul M. A., Nielsen U.K., Shalaby M.R., Adams G.P., Weiner L.M., Marks J.D. Expression of single-chian Fv-Fc fusions in Pichia pastoris. J. Immunol. Methods 2001, 251: 123-135.
Seffens W., Digby D. mRNAs have greater negative folding free energies than shuffled or codon choice randomized sequence. Nucl. Acids Res. 1999, 27: 1578-1584.
Shi X., Karkut T., Chamankahh M., Alting M.M., Hemmingsen S.M., Hegedus D. Optimal conditions for the expression of a single-chain antibody (scFv) gene in Pichia pastoris. Protein Expres. Purif. 2003, 28:321-330.
Shusta E.V., Raines R. T., Pluckthun A, Wittrup K. D. Increasing the secretory capacity of Saccharomyces cerevisiae for production of single-chain antibody fragments. Nat. Biotechnol. 1998, 16: 773-778.
Sinclair G., Choy F. Y. M. Synonymous codon usage bias and the expression of human glucocerebrosidase in the methylotrophic yeast Pichiapastors. Protein Expres. Purif. 2002, 26: 96～105.
Sreekrishna K., R. G. Brankamp, K. E. Kropp, D. T. Blankenship, J. T. Tsay, P. L. Smith, J.D. Wierschke, A.
Subramaniam, L.A. Birkenberger, Strategies for optimal synthesis and secretion of heterologous proteins in the methylotrophic yeast Pichia pastoris. Gene 1997,190: 55-62.
Vad R., E. Nafstad, L.A. Dahl, Gabrielsen O.S. Engineering of a Pichia pastoris expression system for secretion of high amounts of intact human parathyroid hormone. J. Biotechnol. 2005,30:251-260.
Wang J., Shi Y., Liu Y., Hu S., Ma J., Liu J., Chen L. Purification and characterization of a single-chain chimeric anti-pl85 antibody expressed by CHO-GS system. Protein Expres. Purif. 2005,41: 68-76.
Wolff A.M., Hansen O.C., Poulsen U., Madrid S., Stougaard P. Optimization of the production of chondrus crispus hexose oxidase in P. pastoris. Protein Expres. Purif. 2001,22: 189-199.
Woo Y., Liu Y., Mathias A., Stavrou v, Wang Z., Thompson J., Neville D.M. Gene optimization is necessary to express a bivalent anti-human anti-T cell immunotoxin in Pichia pastoris. Protein Expres. Purif. 2002, 25: 270-282.
Xia X. How optimized is the translational machinery in Escherichia coli, Salmonella typphimuriu and Saccharomyces cerevisiae? Genetics 1998,149: 37-44.
Zhao X., K.K. Huo, Li Y. Y. Synonymous codon usage in Pichia pastoris. Chinese J. Biotechnol. 2000,16: 308-311.
Almagro, J. C. (2004) Identification of differences in the specificity-determining residues of antibodies that recognize antigens of different size: implications for the rational design of antibody repertoires. J. Mol. Recognit. 17, 132-143.
Baselga, J., Albanell, J. Mechanism of action of anti-HER2 monoclonal antibodies. Ann. Oncol. Suppll (2001) 35-41.
Bell, C. A., Tynan, J. A., Hart, K.C., Meyer, A.N., Robertson, S.C., Donoghue, D.J. (2002) Rotational Coupling of the Transmembrane and Kinase Domains of the Neu Receptor Tyrosine Kinase. Mol. Biol. Cell. 11, 3589-3599
Bissan A. L., Arthur M. L., Cyrus C., Standard conformations for the canonical structures of immunoglobulins, J. Moi. Bio. 1997, 273: 927-948.
Boyer, C.M., Pusztai, L., Wiener, J. R., Xu, F. J., Dean, G.S, Bast, B.S., O'Briant, K.C., Greenwald, M., Desombere, K.A., Bast, R.C. (1999) Relative cytotoxic activity of immunotoxins reactive with different epitopes on the extracellular domain of the c-erbb-2 (her-2/neu) gene product p185. Int. J. Cancer. 82, 525-531.
Braden, B. C., Poljak, B.J. (1995) Structural features of the reactions between antibodies and protein antigens. FASEB J. 9, 9-16.
Bruniger, A. T., Rice, L.M., (1997) Crystallographic refinement by simulated annealing: methods and applications. Chao G., Cochran J.R., Wittrup K.D., Fine epitope mapping of anti-epidermal growth factor receptor antibodies through random mutagenesis and yeast surface display, J. Mol. Bio., 2004 342, 539-550.
Cho H. S., Mason K., Ramyar K. X., Stanley A. M., Gabelli S. B., Dermey D.W., Leahy D.J., Structure of the extraceilular region of HER2 alone and in complex with the Herceptin Fab, Nature, 2003, 421: 756-760.
Conte, L. L., Chothia, C., Janin, J. (1999) The Atomic Structure of Protein-Protein Recognition Sites. J. Mol. Biol. 285, 2177-2198.
David, R. D., Gerson, H.C. (1996) Interactions of protein antigens with antibodies. Proc. Natl. Acid. Sci. 93, 7-12.
Decanniere, K., Muyldermans, S., Wyns, L. (2000) Canonical Antigen-binding Loop Structures in Immunoglobulins: More Structures, More Canonical Classes? J. Mol. Biol. 300: 83-91.
Franklin M. C., Carey K. D., Vajdos F. F., Leahy D. J, Vos A.M, Sliwkowski M.X., Insights into ErbB2 signaling from the structure of the ErbB2-pertusumab complex. Cancer Cell, 2004, 5:317-327.
Itoh K., Inoue K., Tezuka T., Tada H., Hashimoto Y., Masuko T., Suzuki T., Molecular structual and funtional characterization of tumor suppressive anti-ErbB2 monoclonal antibody by phage display system, J. Biochem., 2003, 133: 239-245.
Jones, T. A., Kjeldgaard, M. (1997) Electron-density map interpretation, Methods Enzymol. 277,173-208.
Klapper, L.N., Vaisman, N., Hurwitz E., Ronit P.K, Yarden Y., Sela, M. A subclass of tumor-inhibitory monoclonal antibodies to ErbB-2/HER blocks crosstalk with growth factor receptors. Oncogene (1997) 14, 2099-2109.
Laskowski, R.A., MacArthur, M.W., Moss, D.S., Thornton, J.M. (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26,283-291.
Le X.F., Amanda M.W., Wiener J., Wu J.Y., Mills G.B., and Bast R.C Jr. Anti-HER2 Antibody and Heregulin Suppress Growth of HER2-Overexpressing Human Breast Cancer Cells through Different Mechanisms. Clin. Cancer Res. 2000,6: 260-270.
L Li, H. Liu, S. Hu, D. Liang, L. Cheng, J. Liu. Soluble Expression and Characterization of Disulfide Bond-rich Subdomains of membrane Protein p 185 in E. coli. Chinese Journal of Biotechnology 2005,21: 590-596.
Longva, K.E., Pedersen N.M., Haslekas, C, Stang, E., Madshus I.H. (2005) Herceptin-induced inhibition of ErbB2 signaling involves reduced phosphorlylation of Akt but not endocytic downr-egulation of ErbB2. Int. J. Cancer 116, 359-367.
Lorenzo, C.D., Palmer, D.B., Piccoli R., Ritter M.A., D'Alession G. (2002) A new human antitumor immunoreagent specific for ErbB2. Clin. Cancer Res. 8,1710-1719.
Neve R.M., Nielsen U.B., Kirpotin D.B., Poul M.A., Marks J.D., Benz C.C. Biological Effects of Anti-ErbB2 Single Chain Antibodies Selected for Internalizing Function, Biochem. Biophys. Res. Commun. 280 (2001) 274-279.
Otwinowski, Z., Mior W. (1997) Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326.
Ritchie, R.W. (2003) Evaluation of protein docking predictions using Hex 3.1 in CAPRI rounds 1 and 2. Proteins: Struc. Func. Bioinform. 52, 98-106.
Vajda, S., Camacho, C.J. Protein-protein docking: is the glass half-full or half-empty? (2004) Trends. Biotech. 22, 111-116.
Veronica M., Anna T., Mauro R., Cyrus C, Arthur M.L, Conformations of the third hypervariable region in the VH domain of immunoglobulins, J. Mol. Bio., 1998,275: 269-294.
Yip Y.M., Novetny J., Edwards M., Ward R.L., Structural analysis of the Erbb2 receptor using monoclonal antibodies: Implications for receptor signaling, Int. J. Cancer 2003,104: 303-309.
Yip, Y.M., Smith, G., Koch, J., Dubel, S., Ward, R. (2001) Identification of epitope regions recognized by tumor inhibitory and stimulatory anti-ErbB2 monoclonal antibodies: Implications for vaccine design. J. Immuno. 166, 5271-5278.
Yum, L.Y., Robyn, L.W. Anti-ErbB2 monoclonal antibodies and ErbB2-directed vaccines. (2002) Cancer. Immunol. Immunother. 50,569-587.
Arocas, V., Castro, H. C., Zingali, R. B, Guillin, M. C, Martin, J. P, Bon, C., Wisner, A., 1994. Molecular cloning and expression of bothrojaracin, a potent thrombin inhibitor from snake venom. European Journal of Biochemistry 248, 550-557.
Atoda, H., Ishikawa, M., Mizuno, H., Morita, T., 1998. Coagulation Factor X-Binding Protein from Deinagkistrodon acutus venom is a Gin domain-binding protein. Biochemistry 37, 17361-17370.
Atoda, H., Ishikawa, M., Yoshihara, E., Sekiya, F., Morita, T., 1995. Blood coagulation factor Ⅸ-binding protein from the venom of Trimeresurusflavoviridis: purification and characterization. Journal of Biochemistry 118, 965-973.
Atoda, H., Yoshida, N., Ishikawa, M., Morita, T., 1994. Binding properties of the coagulation factor Ⅸ/factor Ⅹ-binding protein isolated from the venom of Trimeresurus flavoviraids, European Journal of Biochemistry, 224, 703-708.
Chen Y. L.,Tsai I. H. Functional and sequence Characterization of agkice2 tin, a new glycoprotein Ib antagonist isolated from Agkistrodon acutus venom. Biochem. Biophys. Res. Commun. 1995, 210: 472-477.
Chen, Y. L. and Tsai, I. H., 1996. Functional and Sequence Characterization of Coagulation Factor Ⅸ/Factor
Cheng X., Qian Y., Liu Q., Benjamin X.Y. Lid, Zhang M., Liu J. Purification, Characterization, and cDNA Cloning of aNew Fibrinogenlytic Venom Protein, Agkisacutacin from Agkistrodon acutus Venom. Biochem. Biophys. Res. Commun. 1999, 265: 530-535.
Cregg, J. M., Cereghino, J.L., Shi, J, Higgins, D.R., 2000. Recombinant protein expression in Pichia pastoris. Molecular Biotechnology 16(1), 23-52.
Diacovo T. G., Liddingtonl R.C., Fukuda K., Dogger T.A., Bankston L.A. Cruz M.A. Structural Basis of von Willebrand Factor Activation by the Snake Toxin Botrocetin. Structure 2002, 10: 943-950. Horii K., Okuda D., Morita T., Mizuno H. Crystal Structure of EMS16 in Complex with the Integrin a2-I Domain. J. Mol. Biol. 2004, 341: 519-527.
Fidler, S.L., Young, W., McNatty, K.P., 1998. Expression and secretion of a biologically active glycoprotein hormone, ovine follicle stimulating hormone by Pichia pastoris. Journal of Molecular Endocrinology 21,327-336.
Fukuda, K., Mizuno, H., Atoda, H., Morita, T., 2000. Crystal Structure of Flavocetin-A, a Platelet Glycoprotein Ib-Binding Protein, Reveals a Novel Cyclic Tetramer of C-Type Lectin-like Heterodimers. Biochemistry 39, 1915-1923.
Hirotso, S., Mizuno, H., Fukuda, K., Qi, M.C., Matsui, T., Hamako, J., Morita, T., Titani, K., 2001. Crystal Structure of Bitiscetin, avon Willebrand Factor-Dependent Platelet Aggregation Inducer. Biochemistry 40, 13592-13597.
Jasti, J., Paramasivam, M., Srinivasan, A., Singh, T. P., 2004. Crystal structure of echicetin from Echis carinatus (Indian saw-scaled viper) at 2.4 A° resolution. Journal of Molecular Biology 335, 167-176.
Kalandadze, A., Galleno, M., Foncerrada, L., Strominger, J.L., Wucherpfennig, K.W., 1996. Expression of recombinant HLA-DR.2 molecules: Replacement of the hydrophobic transmembrane region by a leucine zipper dimerization motif allows the assembly and secretion of soluble DR alpha beta heterodimers. Journal of Biological Chemistry 271,20156-20162.
Kawasaki, T., Fujimura, Y., Usami, Y., Suzuki, M., Miura, S., Sakurai, Y., Makita, K., Taniuchi, Y., Hirano, K., Titani, K., 1996. Complete amino acid sequence and identification of the platelet glycoprotein Ib-binding site of jararaca GPIb-BP, a snake venom protein isolated from Bothrops jararaca. Journal of Biological Chemistry 271, 10625-10639.
Lange, S., Schmitt, J., Schmid, R.D., 2001. High-yield expression of the recombinant, atrazine-specific Fab fragment K411B by the methylotrophic yeast Pichia pastoris. Journal of Immunological Methods 255,103-114.
Lee, W.H., Zhuang, Q.Y., Zhang, Y., 2003. Cloning and characterization of a blood coagulation factor IX-binding protein from the venom of Trimeresurus stejnegeri. Toxicon 41, 765-772
Li W., Chen L., Li X., Liu J. A C-type lectin-like protein from Agkistrodon acutus venom binds to both platelet glycoprotein Ib and coagulation factor IX/factorX. Biochem. Biophys. Res. Commun. 2005, 332: 904-912.
Li X., Ji H., Cheng X., Banjamin X.Y. Lid, Ng T.B. Antithrombotic and thrombolytic activities of Agkisacutacin, a snake venom proteinase, in experimental models. General Pharmac. 2002, 35: 179-187.
Lu, Q., Navdaev, A., Clemetson, J.M., Clemetson, K.J., 2005. Snake venom C-type lectins interacting with platelet receptors. Structure-function relationships and effects on haemostasis. Toxicon (in press).
Maita N., Nishio K., Nishimoto E., Matsui T., Shikamoto Y., Morita T., Sadler J.E., Mizuno H. Crystal Structure of von Willebrand Factor Al Domain Complexed with Snake Venom, Bitiscetin: Insight Into Glycoprotein Ib Binding Mechanism Induced By Snake Venom Proteins, J. Biol. Chem. 2003,39: 37777-37781.
Mizuno, H., Fujimoto, Z., Atoda, H., Morita, T., 2001. Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X. Proceedings of the National Academy of Science 98 (13), 7230-7234.
Mizuno, H., Fujimoto, Z., Koizumi, M., Kano, H., Atoda, H., Morita, T., 1997. Structure of coagulation factors IX/X-binding protein, a heterodimer of C-type lectin domains. Nature Structure Biology 4,438-441.
Mizuno, H., Fujimoto, Z., Koizumi, M., Kano, H., Atoda, H., Morita, T., 1999. Crystal structure of coagulation factor IX-binding protein from Habu snake venom at 2.6 A: implication of central loop swapping based on deletion in the linker region. Journal of Molecular Biology 289,103-112.
Monteiro, R.Q, Foguel, D., Castro, H.C., Zingali, R.B., 2003. Subunit dissociation, unfolding, and inactivation of bothrojaracin, a C-type lectin-like protein from snake venom. Biochemistry 42, 509-515.
Morita, T., 2004. Use of snake venom inhibitors in studies of the function and tertiary structure of coagulation factors. International Journal of Hematology 79,123-129.
Ogawa, T., Chijiwa, T., Oda-Ueda, N., Ohno, M., 2005. Molecular diversity and accelerated evolution of C-type lectin-like proteins from snake venom. Toxicon 45,1-14.
Ogunjimi, A.A., Chandler, J.M., Gooding, C.M., 1999. High-level secretory expression of immunologically active intact antibody from the yeast Pichia pastoris. Biotechnology Letters 21, 561-567.
Paaventhan, P., Kong, C, Joseph, J.S., Chung, M.C., Kolatkar, P.R., 2005. Structure of rhodocetin reveals noncovalently bound heterodimer interface. Protein Science 4(1), 169-175.
Peng, M., Holt, J.C., Niewiarowski, S., 1994. Isolation, characterization and amino acid sequence of echicetin b subunit, a specific inhibitor of von willebrand factor and thrombin interaction with glycoprotein Ib. Biochemical and Biophysical Research Communications 205(1), 68-72.
Polgar, J., Magnenat, E.M., Peitsch, M.C., Wells, T.N., Saqi, M.S., Clemetson, K.J., 1997. Amino acid sequence of the alpha subunit and computer modeling of the alpha and beta subunits of echicetin from the venom of Echis carinatus (saw-scaled viper). Biochemical Journal 15(323), 533-537.
Richard, F., Robert, P., Remy, J.J., Martinat, N., Bidart, J.M., Salesse, R., Combarnous, R., 1998. High-level secretion of biologically active recombinant porcine follicle-stimulating hormone by the methylotrophic yeast Pichia pastoris Biochemical and Biophysical Research Communications 245,847-852.
Sen, U., Vasudevan, S., Subbarao, G., McClintock, R.A., Celikel, R., Ruggeri, Z.M., Varughese, K.I, 2001. Crystal structure of the von Willebrand factor modulator botrocetin, Biochemistry 40,345-352.
Sreekrishna, K., Brankamp, R.G., Kropp, K.E., Blankenship, D.T., Tsay, J.T., Smith, P.L., Wierschke, J.D., Subramaniam, A., Birkenberger, L.A., 1997. Strategies for optimal synthesis and secretion of heterologous proteins in the methylotrophic yeast Pichia pastoris. Gene 190,55-62.
Tani, A., Ogawa, T., Nose, T., Nikandrow, N.N., Deshimaru, M., Chijiwa, T., Chang, C.C., Fukumaki, Y., Ohno, M., 2002. Characterization, primary structure and molecular evolution of anticoagulant protein from Agistrodon actus venom. Toxicon 40,803-813.
Wang W.J., Huang T.F.. A novel tetrameric venom protein, agglucetin from Agkistrodon acutus, acts as a glycoprotein Ib agonist. Thromb. Haemost. 2001,86:1077-1186.
X-Binding Protein from the Venom of Echis carinatus leucogaster. Biochemistry 35, 5264-5271.
Xu G., Ulrichts H., Vauterin S., Meyer S., Deckmyn H., Teng M., Niu L. How does agkicetin-C bind on platelet glycoprotein Iba and achieve its platelet effects? Toxicon 2005,45: 561-570.
Xu, X.L., Liu, Q.L., 2001. Binding of anticoagulation factor II from the venom of Agkistrodon acutus with activated coagulation factor X. Toxicon 39,1359-1365.
Xu, X.L., Liu, Q.L., Xie, Y.Sh., Wu, Sh.D., 2000. Purification and characterization of anticoagulation factors from the venom of Agkistrodon acutus. Toxicon 38, 1517-1528.
Yu, H., Xiang, K., Wang, Y., Liu Jo, 2003. Cloning and sequencing of eleven cDNAs of C-type lectin-like protein subunits from Agkistrodon Acutus. Chinese Journal of Biochemistry and Molecular Biology 19(1), 64-70.
刘四九博士论文，2000，皖南尖吻蝮蛇蛇毒抗凝蛋白ACFI-Ⅰ和ACF-2结构与功能关系的研究。
朱忠良博士论文，2003，皖南尖吻蝮蛇蛇毒丝氮酸蛋白酶AaV-SP-Ⅰ和AaV-SP-Ⅱ及蛇毒C性凝集素类似蛋白agkaggrengin，AaACP-A-analogue和AaACP-B-analogue的结构生物学研究。