半乳糖脂的合成、肝靶向研究及利用“点击化学”合成糖缀合物
|
摘要
存在于肝实质细胞表面的无唾液酸糖蛋白受体(ASGPr)是一高效内吞受体,具有高度的组织特异性、高亲和力和高容量的特点,这使得以无唾液酸蛋白受体介导的肝靶向给药系统有望成为可用于临床的肝靶向给药系统。而脂质体作为靶向药物和基因转移的载体,具有良好的生物兼容性、可降解性、无抗原性及多功能性,因而倍受人们的青睐。
鉴于此,为了构建具有肝靶向传递作用的稳定的给药系统,我们以具有肝细胞特异性的ASGPr为靶标,设计了三类新型半乳糖脂作为靶头,脂质体作为药物载体,从而构建半乳糖簇-脂质体-抗癌药物组成的主动的肝靶向载药系统。
本文以半乳糖、胆固醇、氨基酸等为初始原料,经过乙酰基保护与脱保护,糖苷化,缩合以及催化氢化等一系列反应可得到半乳糖合成子6a、4b和6c,同时胆固醇与丁二酸酐反应得到CHS (8)。之后在DCC/NHS或者DIPEA、HOBT、HBTU的催化下,半乳糖合成子与CHS缩合可得到半乳糖-胆固醇偶联物TM 1~3。并通过IR、1H-NMR、13C-NMR、1H-1H COSY、HSQC以及MS对其进行了结构确定;而对于三分支糖脂的合成,由于实验过程中多肽的酯水解时,肽键发生断裂,未得到三分支糖脂。但从活性数据可以看出:一、二分支糖脂肝靶向性效果比较理想,静脉注射30 min后,相对于普通脂质体中的阿霉素,单、双靶头脂质体中的阿霉素在血液中迅速降低,相反在肝脏中的累积则迅速增加,普通脂质体的肝累积仅有23.38%,而单、双靶头修饰的脂质体分别为41.67%、66.43%;并且它们合成更加简便快捷,因此较三分支糖脂更具实用性。
另一方面,由于Cu(I)-介导的1,3-偶极环加成反应具有区域选择性、产率高以及反应条件温和的特点,因此最近几年该反应被广泛用来合成寡糖和糖缀合物,但由于异头叠氮的位阻较大,在一些糖缀合物的合成中产率并不是很理想。
本文我们发展了新的合成策略,将糖基配体连接到氨基酸、芳环以及杂环化合物中,合成了八种糖肽、皂苷等类似物。通过引入连接臂,减少了空间位阻,使反应产率大大提高(≥85%);并且除了g10a的合成外,大部分反应的选择性也比较高。因此,该法可用作糖缀合物的新的合成策略。本论文并对所合成的化合物分别做了IR、1H-NMR、13C-NMR、1H-1H COSY、HSQC以及EA或MS,对目标化合物进行了结构表征;对两种中间产物的单晶还进行了X-射线单晶衍射分析。
由于在g7a的合成中,采用加热回流和类似水热合成两种方法,方法一投料比大,浪费原料,且有副反应发生产率低;而采用方法二降低投料比的同时,高效的合成了g7a (87%);同时,由于加热回流中的副产物g7a″的产量较大(41%),我们对其进行了结构分析,发现了一个新型的杂环化合物,并对其反应历程进行了探讨。
On the surface of parenchymal cells, there exists an unique receptor protein, the galactose (Gal)- or N-acetylgalactosamine (GalNAc)-recognizing asialoglycoprotein receptor (ASGPr). In view of its exclusive and abundant presence on hepatocytes, and because of its high-affinity and high rate of internalization, the ASGPr was considered a promising candidate target in many drug carrier studies.
On this viewpoint, in order to constitute targeted drug delivery system, three series of cholesterylated galactosides were designed as the targetable ligand of liposomal carriers for hepatocytes in this thesis.
Monoantennary and diantennary galactoside synthons (6a, 4b and 6c) were obtained through several chemistry reactions (protection, deprotection, glycosidation, conjugation and catalytic hydrogenation et cetera), while 4-(5-cholesten-3-yloxy)-4-oxo-butanoic acid (CHS) was obtained through the reaction of cholesterol with succinic anhydride. After the reaction between galactoside synthons and CHS under the catalysis of NHS, DCC or DIPEA, HOBT and HBTU, three target galactolipids (TM 1~3) were gained. The structures of the synthesized compounds are confirmed by means of IR, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC and MS. But triantenary galactosylated lipids were not synthesized because of alkaline hydrolysis of peptides. But the data of hepatic targeting test in mouse in vivo show that monoantennary and diantennary galactosylated lipids modified liposomes were better in liver targeting than control liposome. Compared with the injection of doxorubicin (Dox) encapsulated in control liposome (CL DOX), the plasma concentration of DOX encapsulated in monoantennary liposome (MGal DOX) and diantennary liposome (DGal DOX) decreased significantly at 30 min after intravenous injection. In contrast, the liver accumulation of MGal DOX or DGal DOX was up to 41.67% and 66.43% of the total injected dose within 30min, respectively, while the accumulation of CL DOX was relatively lower (23.38%). This shows the hepatic targeting effects of MGal DOX and DGal DOX was significantly higher than that of CL DOX. Moreover, monoantennary and diantennary galactosylated lipids can be facilely and simplely synthesized, so they are more practicable in clinic.
Application Cu(I)-mediated 1,3-dipolar cycloaddition to oligosaccharides and glycoconjugates has recently begun, and most of the reports are concerned with the use of anomeric azides. Because of steric hindrance, the yield of such reaction is usually low, which limited its application.
Subsequently, we have developed several practical strategies for the ligation of sugar to amino acids, steroidal, aryl or heterocyclic compounds. Eight target compounds were obtained as the mimics of glycopeptide, saponin or other glycoconjugates. The yields of most reactions were more than 85% with complete regioselectivity except for compound g10a. All products were confirmed by IR, 1H NMR, 13C NMR, DEPT, HSQC and EA or Ms; and two intermediate products were cultured to single crystals and confirmed by X-Ray difference reflections.
In addition, the synthesis of compound g7a under reflux needs high molar ratio and wastes materials. Moreover, an unexpected side reaction was found in this reaction. The yield (48%) was very low, which is almost equal to the by-product (41%). Then we improved this experiment, proceeded the reaction in Teflon-lined stainless steel autoclave, and compound g7a was synthesized efficiently (87%) with low molar ratio. Meanwhile, a new heterocyclic compound g7a" was unexpectedly discovered and confirmed by 1H NMR, 13C NMR and Ms, and the mechanism of this reaction was studied.
鉴于此,为了构建具有肝靶向传递作用的稳定的给药系统,我们以具有肝细胞特异性的ASGPr为靶标,设计了三类新型半乳糖脂作为靶头,脂质体作为药物载体,从而构建半乳糖簇-脂质体-抗癌药物组成的主动的肝靶向载药系统。
本文以半乳糖、胆固醇、氨基酸等为初始原料,经过乙酰基保护与脱保护,糖苷化,缩合以及催化氢化等一系列反应可得到半乳糖合成子6a、4b和6c,同时胆固醇与丁二酸酐反应得到CHS (8)。之后在DCC/NHS或者DIPEA、HOBT、HBTU的催化下,半乳糖合成子与CHS缩合可得到半乳糖-胆固醇偶联物TM 1~3。并通过IR、1H-NMR、13C-NMR、1H-1H COSY、HSQC以及MS对其进行了结构确定;而对于三分支糖脂的合成,由于实验过程中多肽的酯水解时,肽键发生断裂,未得到三分支糖脂。但从活性数据可以看出:一、二分支糖脂肝靶向性效果比较理想,静脉注射30 min后,相对于普通脂质体中的阿霉素,单、双靶头脂质体中的阿霉素在血液中迅速降低,相反在肝脏中的累积则迅速增加,普通脂质体的肝累积仅有23.38%,而单、双靶头修饰的脂质体分别为41.67%、66.43%;并且它们合成更加简便快捷,因此较三分支糖脂更具实用性。
另一方面,由于Cu(I)-介导的1,3-偶极环加成反应具有区域选择性、产率高以及反应条件温和的特点,因此最近几年该反应被广泛用来合成寡糖和糖缀合物,但由于异头叠氮的位阻较大,在一些糖缀合物的合成中产率并不是很理想。
本文我们发展了新的合成策略,将糖基配体连接到氨基酸、芳环以及杂环化合物中,合成了八种糖肽、皂苷等类似物。通过引入连接臂,减少了空间位阻,使反应产率大大提高(≥85%);并且除了g10a的合成外,大部分反应的选择性也比较高。因此,该法可用作糖缀合物的新的合成策略。本论文并对所合成的化合物分别做了IR、1H-NMR、13C-NMR、1H-1H COSY、HSQC以及EA或MS,对目标化合物进行了结构表征;对两种中间产物的单晶还进行了X-射线单晶衍射分析。
由于在g7a的合成中,采用加热回流和类似水热合成两种方法,方法一投料比大,浪费原料,且有副反应发生产率低;而采用方法二降低投料比的同时,高效的合成了g7a (87%);同时,由于加热回流中的副产物g7a″的产量较大(41%),我们对其进行了结构分析,发现了一个新型的杂环化合物,并对其反应历程进行了探讨。
On the surface of parenchymal cells, there exists an unique receptor protein, the galactose (Gal)- or N-acetylgalactosamine (GalNAc)-recognizing asialoglycoprotein receptor (ASGPr). In view of its exclusive and abundant presence on hepatocytes, and because of its high-affinity and high rate of internalization, the ASGPr was considered a promising candidate target in many drug carrier studies.
On this viewpoint, in order to constitute targeted drug delivery system, three series of cholesterylated galactosides were designed as the targetable ligand of liposomal carriers for hepatocytes in this thesis.
Monoantennary and diantennary galactoside synthons (6a, 4b and 6c) were obtained through several chemistry reactions (protection, deprotection, glycosidation, conjugation and catalytic hydrogenation et cetera), while 4-(5-cholesten-3-yloxy)-4-oxo-butanoic acid (CHS) was obtained through the reaction of cholesterol with succinic anhydride. After the reaction between galactoside synthons and CHS under the catalysis of NHS, DCC or DIPEA, HOBT and HBTU, three target galactolipids (TM 1~3) were gained. The structures of the synthesized compounds are confirmed by means of IR, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC and MS. But triantenary galactosylated lipids were not synthesized because of alkaline hydrolysis of peptides. But the data of hepatic targeting test in mouse in vivo show that monoantennary and diantennary galactosylated lipids modified liposomes were better in liver targeting than control liposome. Compared with the injection of doxorubicin (Dox) encapsulated in control liposome (CL DOX), the plasma concentration of DOX encapsulated in monoantennary liposome (MGal DOX) and diantennary liposome (DGal DOX) decreased significantly at 30 min after intravenous injection. In contrast, the liver accumulation of MGal DOX or DGal DOX was up to 41.67% and 66.43% of the total injected dose within 30min, respectively, while the accumulation of CL DOX was relatively lower (23.38%). This shows the hepatic targeting effects of MGal DOX and DGal DOX was significantly higher than that of CL DOX. Moreover, monoantennary and diantennary galactosylated lipids can be facilely and simplely synthesized, so they are more practicable in clinic.
Application Cu(I)-mediated 1,3-dipolar cycloaddition to oligosaccharides and glycoconjugates has recently begun, and most of the reports are concerned with the use of anomeric azides. Because of steric hindrance, the yield of such reaction is usually low, which limited its application.
Subsequently, we have developed several practical strategies for the ligation of sugar to amino acids, steroidal, aryl or heterocyclic compounds. Eight target compounds were obtained as the mimics of glycopeptide, saponin or other glycoconjugates. The yields of most reactions were more than 85% with complete regioselectivity except for compound g10a. All products were confirmed by IR, 1H NMR, 13C NMR, DEPT, HSQC and EA or Ms; and two intermediate products were cultured to single crystals and confirmed by X-Ray difference reflections.
In addition, the synthesis of compound g7a under reflux needs high molar ratio and wastes materials. Moreover, an unexpected side reaction was found in this reaction. The yield (48%) was very low, which is almost equal to the by-product (41%). Then we improved this experiment, proceeded the reaction in Teflon-lined stainless steel autoclave, and compound g7a was synthesized efficiently (87%) with low molar ratio. Meanwhile, a new heterocyclic compound g7a" was unexpectedly discovered and confirmed by 1H NMR, 13C NMR and Ms, and the mechanism of this reaction was studied.
引文
[1]张晓茹,几种糖簇化合物的合成及其活性研究,中国海洋大学,2003
[2]俞飙,金城,糖的化学和生物科学,21世纪有机化学发展战略,杜灿屏,刘鲁生,张恒主编,第一版,北京,化学工业出版社,2002: 298-306
[3] Haltiwanger R. S., Lowe J. B., Role of glycosylation in development, Annu. Rev. Biochem., 2004, 73: 491-537
[4] Cobb B. A., Wang Q., Tzianabos A. O. et al, Polysaccharide processing and presentation by the MHCII pathway, Cell, 2004, 117: 677-687
[5] Adeoye O. M., Ferrell R. E., Kirshner M. A. et al, 1-Acid Glycoprotein in Late-Life Depression: Relationship to Medical Burden and Genetics, J. Geriatr Psychiatry Neurol., 2003, 16(4): 235-239
[6] Swingler S., Brichacek B., Jacque J. M. et al, HIV-I Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection, Nature, 2003, 424: 213-219
[7] Kim H. M., Kim L. J., Danishefsky S. J., Total Syntheses of Tumor-Related Antigens N3: Probing the Feasibility Limits of the Glycal Assembly Method, J. Am. Chem. Soc., 2001, 123(1): 35-48
[8] Kolter T., Sandhoff K., Sphingolipids-their Metabolic Pathways and the Pathobiochemistry of Neurodegenerative Diseases, Angew. Chem. Int. Ed., 1999, 38(11): 1532-1568
[9] Rademacher T. W., Parekh R. B., Dwek R. A., Glycobiology, Annu. Rev. Biochem., 1988, 57: 785-838
[10] Lemieux R. U., The origin of the specificity in the recognition of oligosaccharides by proteins, Chem. Soc. Rev., 1989, 18: 347-374
[11] Kunz H., Glyciopeptides of biological interest: A challenge for chemical synthsis, Pure&Appl. Chem., 1993, 65(6): 1223-1232
[12] Zhao N., Kumar N., Neuenschwander K. et al, Quaternary Ammonium Salts as Chromophores for Exciton-Coupled Circular Dichroism: Absolute Configuration of Hypocholesterolemic Quinuclidines, J. Am. Chem. Soc., 1995, 117(29): 7844-7845
[13] Matile S., Berova N., Nakanishi K. et al, Porphyrins: Powerful Chromophores for Structural Studies by Exciton-Coupled Circular Dichroism, J. Am. Chem. Soc., 1995, 117(26): 7021-7022
[14]尚遂存,兰淑琴等,中草药食品抗氧化荆的筛选,天然产物研究与开发,1994, 6(1): 36-38
[15] Lee L. V., Mitchell M. L., Huang S. J. et al, A Potent and Highly Selective Inhibitor of Human
[16] Wilkinson B. L., Bornaghi L. F., Houston T. A. et al, Carbonic Anhydrase Inhibitors: Inhibition of Isozymes I, II, and IX with Triazole-Linked O-Glycosides of Benzene Sulfonamides, J. Med. Chem., 2007, 50(7): 1651-1657
[17] Asano N., Glycosidase inhibitors: update and perspectives on practical use, Glycobiology, 2003, 13(10): 93R-104R
[18] Jean M. H., Elsen V. D. , Kuntz D. A. et al, Structure of Golgiα-mannosidase II: a target for inhibition of growth and metastasis of cancer cells, The EMBO Journal, 2001, 20(12): 3008-3017
[19] Rossi L. L., Basu A., Glycosidase inhibition by 1-glycosyl-4-phenyl triazoles, Bioorg. Med. Chem. Lett., 2005, 15: 3596-3599
[20] Wang J., Uttamchandani M., Li J. Q. et al, Rapid Assembly of Matrix Metalloprotease Inhibitors Using Click Chemistry, Org. Lett., 2006, 8(17): 3821-3824
[21] Bertozzi C. R., Kiessling L. L., Carbohydrates and Glycobiology-Chemical Glycobiology, Science, 2001, 291(23): 2357-2364
[22] Davis B. G., Recent developments in glycoconjugate, J. Chem. Soc. Perkin Trans. 1, 1999: 3215-3237
[23] Bezou?ka K., Design functional evaluation and Biomedical applications of carbohydrate dendrimers (glycodendrimers), Rev. Mole. Biotech., 2002, 90: 269-290
[24] Mammen M., Choi S. K., Whitesides G. M., Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors, Angew. Chem. Int. Ed., 1998, 37: 2754-2794
[25] Patri A. K., Kukowska-Latallo J. F., Baker J. R., Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion comples, Adv. Drug Deliv. Rev., 2005, 57: 2203-2214
[26] Arcadio C., Pieter R. C., Recent advances in liposome technologies and their applications for systemic gene delivery, Adv. Drug Deliv. Rev., 1998, 30: 73-83
[27] Jain A. K., Panchagnula R., Skeletal drug delivery systems, Int. J. Pharm., 2000, 206: 1-12
[28] Spiess M., The Asialoglycoprotein Receptor: A Model for Endocytic Transport Receptors, Biochemistry, 1990, 29(43): 10009-10018
[29] Drickamer K., Biology of animal lectins, Annu. Rev. Cell Biol., 1993, 9: 237-264
[30] Meier M., Bider M. D., Malasherkevich V. N. et al, Crystal structure of the carbohudrate recognition domain of the H1 subunite of the asialoglycoprotein receptor, J. Mol. Biol., 2000, 300: 857-865
[31] Bider M. D., Spiess M., Ligand-induced endocytosis of the asialoglycoprotein receptor: evidencefor heterogeneity in subunit oligomerization, FEBS Lett., 1998: 37-41
[32] Vera D. R., Stadalnik R. C., Krohn K. A., Technetium-99m galactosylneoglycoalbumin: preparation and preclinical studies, J. Nucl. Med., 1985, 26(10): 1157-1167
[33] Nishikawa M., Kamijo A., Fujita T. et al, Synthesiss and pharmacokinetics of a new liver-specific carrier, glycosylated Carboxymethyl-Dextran, and its application to drug targeting , Pharma Res., 1993, 10(9): 1253-1261
[34] Goto M., Yura H., Chang C. W. et al, Lactose-carrying polystyrene as a drug carrier: investigation of body distrubutions to parenchymal liver cells using 125I-labelled lactose carrying polystyrene, J. Controlled Release, 1994, 28(1-3): 223-233
[35]管昌田,钟裕国,梁正路等,糖基干扰素的合成及其肝靶向性的研究,中华核医学杂志,1996, 16 (I): 58-59
[36] Nishikawa M., Miyazaki C., Yamashita F. et al, Galactosylated proteins are recognized by the liver according to the surface density of galactose moieties, Am. J. Physiol., 1995, 268: 6849-6856
[37]梁正路,付辛,管昌田等,双糖密度半乳糖基胰岛素的合成及肝靶向性初步研究,华西医大学报,2000, 31(1): 1-4
[38] Zhang X., Simmons C. G., Corey D. R., Liver cell specific targeting of peptide nucleic acid oligomers, Bioorg. Med. Chem. Lett., 2001, 11(10): 1269-1272
[39] Kawakami S., Munakata C., Funotos S. et al, Targeted delivery of prostaglandin EI to hepatocytes using galactosylated liposomes, J. Drug Target, 2000, 8(3): 137-142
[40] Kawakami S., Yamashita F., Nishikawa M. et al, Asialoglycoprotein receptor-mediated gene transfer using novel galactosylated cationic liposomes, Biochem. Biophys. Res. Commun., 1998, 252: 78-83
[41]海俐,无唾液酸糖蛋白受体介导的肝靶向脂质体配体的设计、合成及靶向性研究,四川大学,2006
[42] Rensen P. C. N., Sliedregt L. A. J. M., Perns M. et al, Determination of the upper size limit for uptake and processing of ligands by the asialoglycoprotein receptor on hepatocytes in vitro and in vivo, J. Biochem. Chem., 2001, 276(40): 37577-37584
[43] Sliedregt L. A. J. M., Rensen P. C. N., Rump E. T. et al, Design and synthesis of novel amphiphilic dendritic galactosides for selective targeting of liposomes to the hepatic asialoglycoprotein receptor, J. Med. Chem., 1999, 42(4): 609-618
[44] Rensen P. C. N., Leeuwen S. H. V., Sliedregt L. A. J. M. et al, Design and Synthesis of Novel N-Acetylgalactosamine-Terminated Glycolipids for Targeting of Lipoproteins to the Hepatic Asialoglycoprotein Receptor, J. Med. Chem., 2004, 47(23): 5798-5808
[45] Rensen P. C. N., Sliedregt L. A. J. M., Santbrink P. J. V., Stimulation of Liver-Directed Cholesterol Flux in Mice by Novel N-Acetylgalactosamine-Terminated Glycolipids with High Affinity for the Asialoglycoprotein Receptor, Arterioscler. Thromb. Vasc. Biol., 2006, 26: 169-175
[46] Lee Y. C., Townsend R. R., Hardy M. R. et al, Binding of synthetic oligosaccharides to the hepatic Gal/GalNAc lectin. Dependence on fine structural features, J. Biol. Chem., 1983, 258: 199-202
[47] Biessen E. A. L., Beuting D. M., Roelen H. C. P. F. et al, Synthesis of Cluster Galactosides with High Affinity for the Hepatic Asialoglycoprotein Receptor, J. Med. Chem., 1995, 38(9): 1538-1546
[48] Sliedregt L. A. J. M., van Rossenberg S. M. W., Autar R. et al, Design and synthesis of a multivalent homing device for targeting to murine CD22, Bioorg. Med. Chem., 2001, 9(1): 85-97
[49] Ren T., Zhang G., Liu D., Synthesis of galactosyl compounds for targeted gene delivery, Bioorg. Med. Chem., 2001, 9: 2969-2978
[50] Iobst S. T., Drickamer K., Selective Sugar Binding to the Carbohydrate Recognition Domains of the Rat Hepatic and Macrophage Asialoglycoprotein Receptors, J. Biol. Chem., 1996, 271: 6686-6693
[51]王葆仁,有机合成反应(上册),北京:科学出版社,1982: 418-452
[52] Huisgen R., Mechanism of 1,3-dipolar cycloadditions, J. Org. Chem., 1968, 33(6): 2291-2297
[53] Kolb H. C., Finn M. G., Sharpless K. B., Click Chemistry: Diverse Chemical Function from a Few Good Reactions. Angew. Chem. Int. Ed., 2001, 40: 2004-2021
[54]李娟,段明,张烈辉等,点击化学及其应用,化学进展,2007, 19 (11): 1754-1760
[55] Patton G. C., Development and Applications of Click Chemistry, [2006-12-11]. http://forum.e2002. com/read.php? tid=78386&fpage=0 &toread=&page=1
[56] Franke R., Doll C., Eichler J., Peptide ligation through click chemistry for the generation of assembled and scaffolded peptides, Tetrahedron Lett., 2005, 46: 4479-4482
[57] Rossi L. L., Basu A., Glycosidase inhibition by 1-glycosyl-4-phenyl triazoles, Bioorg. Med. Chem. Lett., 2005, 15: 3596-3599
[58] Pérez-Balderas P., Ortega-Muňoz M., Santoyo-González F., et al. Multivalent Neoglyco- conjugates by Regiospecific Cycloaddition of Alkynes and Azides Using Organic-Soluble Copper Catalysts, Org. Lett., 2003, 5: 1951-1954
[59] Arosio D., Bertoli M., Manzoni L. et al, Click chemistry to functionalise peptidomimetics, Tetrahedron Lett., 2006, 47: 3697-3700
[60] Radic Z., Manetsch R., Sharpless K. B. et al, Molecular basis of interactions of cholinesteraseswith tight binding inhibitors, Chemico-Biological Interactions, 2005, 157/158: 133-141
[61] Manetsch R., Krasiński A., Radic Z. et al, In Situ Click Chemistry: Enzyme Inhibitors Made to Their Own Specifications, J. Am. Chem. Soc., 2004, 126: 12809-12018
[62] Weber L., Drug Discovery Today, 2004, 1: 261-267
[63] Speers A. E., Adam G. C., Cravatt B. F, Activity-Based Protein Profiling in Vivo Using a Copper(I)-Catalyzed Azide-Alkyne [3+2] Cycloaddition, J. Am. Chem. Soc., 2003, 125: 4686-4687
[64] Speers A. E., Cravatt B. F., Profiling Enzyme Activities In Vivo Using Click Chemistry Methods, Chem. Biol., 2004, 11: 535-546
[65] Gao H. F., Matyjaszewski F., Synthesis of Star Polymers by a Combination of ATRP and the "Click" Coupling Method, Macromolecules, 2006, 39: 4960-4965
[66] Ossipov D. A., Hilborn J., Poly(vinyl alcohol)-Based Hydrogels Formed by "Click Chemistry", Macromolecules, 2006, 39: 1709-1718
[67] Vogt A. P., Sumerlin B. S., An Efficient Route to Macromonomers via ATRP and Click Chemistry, Macromolecules, 2006, 39: 5286-5292
[68] Liu Q. C., Chen Y. M., Synthesis of well-defined macromonomers by the combination of atom transfer radical polymerization and a click reaction, J. Polym. Sci., Part A: Polym. Chem., 2006, 44: 6103-6113
[69] Lee J. W., Kim J. H., Jin S. H. et al, Synthesis of Fréchet type dendritic benzyl propargyl ether and Fréchet type triazole dendrimer, Tetrahedron, 2006, 62: 894-900
[70] Li H. M., Cheng F. Y., Adronov A., Functionalization of Single-Walled Carbon Nanotubes with Well-Defined Polystyrene by "Click" Coupling, J. Am. Chem. Soc., 2005, 127: 14518- 14524
[71] Oreilly R. K., Joralemon M. J., Hawker C. J. et al, Facile Syntheses of Surface-functionalized Micelles and Shell Cross-linked Nanoparticles, J. Polym. Sci., Part A: Polym. Chem., 2006, 44: 5203-5217
[72] Such G. K., Quinn J. F., Caruso F. et al, Assembly of Ultrathin Polymer Multilayer Films by Click Chemistry, J. Am. Chem. Soc., 2006, 128: 9318-9319
[73] Diaz D. D., Fokin V. V., Sharpless K. B. et al, chemistry in materials synthesis. 1. Adhesive polymers from copper-catalyzed azide-alkyne cycloaddition, J. Polym. Sci., Part A: Polym. Chem., 2004, 42: 4392-4403
[74] Slater M., Snauko M., Svec F., Frechet J. M. J., "Click Chemistry" in the Preparation of Porous Polymer-Based Particulate Stationary Phases forμ-HPLC Separation of Peptides and Proteins, Anal. Chem., 2006; 78(14): 4969-4975
[1] Hashida M., Nishikawa M., Takakura Y. J., Hepatic targeting of drugs and proteins by chemical modification, Controlled Release, 1995, 36: 99-107
[2] Gestwicki J. E., Cairo C. W., Strong L. E., Influencing Receptor-Ligand Binding Mechanisms with Multivalent Ligand Architecture, J. Am. Chem. Soc., 2002, 124(50): 14922-14933
[3] Frisch B., Carrière M., Largeau C. et al, A New Triantennary Galactose-Targeted PEGylated Gene Carrier, Characterization of Its Complex with DNA and Transfection of Hepatoma Cells, Bioconjugate Chem., 2004, 15: 754-764
[4] Sharma A., Sharma U. S., Liposomes in drug delivery: progress and limitations, Inter. J. Pharma., 1997, 154: 123-140
[5] Harashima H., Kiwada H., Liposomal targeting and drug delivery: kinetic consideration, Adv. Drug Delivery Rev., 1996, 19: 425-444
[6] Davis B. G., Recent developments in glycoconjugate, J. Chem. Soc., Perkin Trans. 1, 1999: 3215-3237
[7] Bezou?ka K., Design functional evaluation and Biomedical applications of carbohydrate dendrimers (glycol-dendrimers), Reviews in Molecular Biotech., 2002, 90: 269-290
[8] Rensen P. C. N., Sliedregt L. A. J. M., Ferns M. et al, Determination of the Upper Size Limit for Uptake and Processing of Ligands by the Asialoglycoprotein Receptor on Hepatocytes in Vitro and in Vivo, J Bio. Chem., 2001, 276(40): 37577-37584
[9] Langer P., Ince S. J., Ley S. V., Assembly of dendritic glycocluster from monomeric mannose building blocks, J. Chem. Soc., Perkin Trans 1, 1998, 23: 3913-3915
[10] Zanini D., Roy R., Novel Dendriticα-Sialosides: Synthesis of Glycodendrimers Based on a 3,3’-Iminobis (propylamine) Core, J. Org. Chem., 1996, 61: 7348-7354
[11] Ashton P. R., Boyd S. E., Stoddart J. F. et al, Synthesis of Glycodendrimers by Modification of Poly(propylene imine) Dendrimers, Chem. Eur. J., 1997, 6: 974-984
[12] Roy R., Saha U. K., Rational design of multivalent glycoconjugate ligands and synthesis of libraries of conformationally flexible rotamers of poly-N-linked lactosyl glycines, Chem. Commun., 1996, 2: 201-202
[13]孔繁祚,糖化学,主编朱清时,北京:科学出版社,2005: 342-343.
[14] Kiessling L. L., Gestwicki J. E., Strong L. E., On the hepatocellular surface in mice lacking theminor receptor subunit, Curr. Opin. Chem. Biol., 2000, 4: 696-703
[15] Brian S., Furniss, Antony J. et al, Vogel′s Textbook of Practical Organic Chemistry, Fifth Edition, London: Longman Science & Technical World Publishing Corp, 1989: 875
[16] Zhang X. R., Li Y. X., Chu S. D., et al, Synthesis of Glutamic Acid-based Cluster Galactosides and Their Binding Affinities with Liver Cells, Chin. J. Chem., 2004, 22: 482-486
[17] Lee R. T., Lee Y. C., Facile Synthesis of a High-Affinity Ligand for Mammalian Hepatic Lectin Containing Three Terminal N-Acetylgalactosamine Residues, Bioconjugate Chem., 1997, 8: 762-765
[18] Wang S. N., Deng Y. H., Xu H. et al, Synthesis of a novel galactosylated lipid and its application to the hepatocyte-selective targeting of liposomal doxorubicin, Eur. J. Pharma. Biopharm., 2006, 62: 32-38
[19] Chwarfz H., Bumpus F. M., Page I. H., Synthesis of a Biologically Active Octapeptide Similar to Natural Isoleucine Angiotonin Octapeptide, J. Am. Chem. Soc., 1957, 5: 5697-5703
[20] Hanby W. E., Waley S. G., Watson J., Synthetic Polypeptides. Part II. Polyglutamic Acid, J. Am. Chem. Soc., 1950, 632: 3239-3249
[21] Jorba X., Gill I., Vulfson E. N., Enzymatic Synthesis of the Delicious Peptide Fragments in Eutectic Mixtures, J. Agric. Food Chem., 1995, 43: 2536-2541
[22] Rodriguez M., Fulcrand P., Laur J. et al, Synthesis of Gastrin Antagonists, Analogues of the C-Terminal Tetrapeptide of Gastrin, by Introduction of aβ-Homo Residue, J. Med. Chem., 1989, 32: 522-528
[1]潘国宗主编,现代胃肠病学,北京,科技出版社,1998: 504-514
[2] Andrea T., Christian W., Genes involved in hepatocellular carcinoma: deregulation in cell cycling and apoptosis, Virchows Arch., 2002, 440: 345-352
[3] Poon R. T., Fan S. T., Tsang F. H. et al, Locoregional therapies hepatocellular carcinoma: cricital review from the surgeon's perspective, Ann. Surg., 2002, 235(4): 466-486
[4] Dizon D. S., Kemeny N. E., Intrahepatic arterial infusion of chemotheraphy: clinical results, Semin. Oncol., 2002, 29(2): 126-135
[5]叶胜龙,肝癌的非手术治疗,现代肿瘤医学杂志,1994, 3 (2): 129-130
[6] http://www.avantilipids.com/Liposomes.asp
[7] Crommclin D. J. A., Liposomes as carries for drugs and antigens approaches to preserve their long term stability, Drugs Dev. Pharm., 1994, 20(4): 540-551
[8] Harashima H., Kiwada H., Liposomal targeting and drug delivery: kinetic consideration, Adv. Drug Delivery Rev., 1996, 19: 425-444
[9] Sharma A., Sharma U. S., Liposomes in drug delivery: progress and limitations, Inter. J. Pharma., 1997, 154: 123-140
[10] Hashida M., Akamatsu K., Nishikava M. et al, Design of polymeric prodrugs of prostaglandin E-1 having galactose residue for hepatocyte targeting, J. Controlled Release, 1999, 62: 253-262
[11] Vrueh R. L. A., Rump E. T., Bilt E. V. et al, Carrier-mediated delivery of 9-(2-phosphonyl- methoxyethyl) adenine to parenchymal liver cells: A novel therapeutic approach for hepatitis B, Antimicrob. Agents Chemother., 2000, 44: 477-483
[12] Cho C. S., Cho K. Y., Park I. J. et al, Receptor-mediated delivery of all transretinoic acid to hepatocyte using poly(L-lactic acid) nanoparticles coated with galactose-carrying polystyrene, J. Controlled Release, 2001, 77: 7-15
[13] Kassab R., Parrot-Lopez H., Fessi H. et al, Molecular recognition by Kluyveromyces of amphotericin-loaded, galactose-tagged, poly (lactic acid) microspheres, Bioorg. Med. Chem., 2002, 10: 1767-1775
[14] Ishida E., Managit C., Kawakami S. et al, Biodistribution characteristics of galactosylated emulsions and incorporated probucol for hepatocyte-selective targeting of lipophilic drugs in mice, Pharm. Res., 2004, 21: 932-939
[15] Nag A., Ghosh P. C., Assessment of targeting potential of galactosylated and mannosylatedsterically stabilized liposomes to different cell types of mouse liver, J. Drug Target., 1999, 6: 427-438
[16] Kawakami S., Wong J., Sato A., Hattori Y. et al, Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice, Biochim. Biophys. Acta., 2000, 1524: 258-265
[17] Hassane F. S., Frisch B., Schuber F., Targeted Liposomes: Convenient Coupling of Ligands to Preformed Vesicles Using“Click Chemistry”, Bioconjugate Chem., 2006, 17: 849-854
[18] Gage M., Jain N. K., Reduced hematopoietic toxicity, enhanced cellular uptake and altered pharmacokinetics of azidothymidine loaded galactosylated liposomes, J. Drug Targeting, 2006, 14(1): 1-11
[19] Berna M., Dalzoppo D., Pasut G. et al, Novel Monodisperse PEG-Dendrons as New Tools for Targeted Drug Delivery: Synthesis, Characterization and Cellular Uptake, Biomacromolecules 2006, 7: 146-153
[20] Kawakami S., Munakata C., Fumoto S., Novel Galactosylated Liposomes for Hepatocyte- Selective Targeting of Lipophilic Drugs, J. Pharma. Sci., 2001, 90(2): 105-113
[21] Murao A., Nishikawa M., Managit C. et al, Targeting Efficiency of Galactosylated Liposomes to Hepatocytes in Vivo: Effect of Lipid Composition, Pharma. Res., 2002, 19(12): 1808-1814
[22] Managit C., Kawakami S., Yamashita F. et al, Effect of Galactose Density on Asialoglycoprotein Receptor-Mediated Uptake of Galactosylated Liposomes, J. Parma. Sci., 2005, 94(10): 2266-2275
[23] Ishida E., Managit C., Kawakami S. et al, Biodistribution characteristics of galactosylated emulsions and incorporated probucol for hepatocyte-selective targeting of lipophilic drugs in mice, Pharm. Res., 2004, 21: 932-939
[24] Kaiser N., Kimpfler A., Massing U. et al, 5-Fluorouracil in vesicular phospholipid gels for anticancer treatment: entrapment and release properties, Int. J. Pharm., 2003, 256: 123-131
[25] Mayer L. D., Tai L .C., Bally M. B. et al, Characterization of liposomal systems containing doxorubicin entrapped in response to pH gradients, Biochim. Biophys. Acta, 1990, 1025: 143-151
[26] Wang S. N., Deng Y. H., Xu H. et al, Synthesis of a novel galactosylated lipid and its application to the hepatocyte-selective targeting of liposomal doxorubicin, Eur. J. Pharma. Biopharm., 2006, 62: 32-38
[27] Sliedregt L. A. J. M., Rensen P. C. N., Rump E. T. et al, Design and Synthesis of Novel Amphiphilic Dendritic Galactosides for Selective Targeting of Liposomes to the Hepatic Asialoglycoprotein Receptor, J. Med. Chem., 1999, 42: 609-618
[28] Rensen P. C. N., Sliedregt L. A. J. M., Perns M. et al, Determination of the upper size limit for uptake and processing of ligands by the asialoglycoprotein receptor on hepatocytes in vitro and invivo, J. Biochem. Chem., 2001, 276(40): 37577-37584
[29] Rensen P. C. N., Leeuwen S. H. V., Sliedregt L. A. J. M. et al, Design and Synthesis of Novel N-Acetylgalactosamine-Terminated Glycolipids for Targeting of Lipoproteins to the Hepatic Asialoglycoprotein Receptor, J. Med. Chem., 2004, 47(23): 5798-5808
[30] Rensen P. C. N., Sliedregt L. A. J. M., Santbrink P. J. V. et al, Stimulation of Liver-Directed Cholesterol Flux in Mice by Novel N-Acetylgalactosamine-Terminated Glycolipids With High Affinity for the Asialoglycoprotein Receptor, Arterioscler. Thromb. Vasc. Biol., 2006, 26: 169-175
[31] Perouzel E., Jorgensen M. R., Keller M., Synthesis and Formulation of Neoglycolipids for the Functionalization of Liposomes and Lipoplexes, Bioconjugate Chem., 2003, 14: 884-898
[32] Merwin J. R., Noell G. S., Wendy L. et al, Targeted Delivery of DNA Using YEE(GalNAcAH)3, a Synthetic Glycopeptide Ligand for the Asialoglycoprotein Receptor, Bioconjugate Chem., 1994, 5: 612-620
[33] Singh M., Ariatti M., Targeted gene delivery into HepG2 cells using complexes containing DNA, cationized asialoorosomucoid and activated cationic liposomes, J. Controlled Release, 2003, 92: 383-394
[34] Kawakami S., Yamashita F., Nishikawa M. et al, Asialoglycoprotein Receptor-Mediated Gene Transfer Using Novel Galactosylated Cationic Liposomes, Biochem. Biophys. Res. Commu., 1998, 252(1): 78-83
[35] Frisch B., Carrière M., Largeau C. et al, A New Triantennary Galactose-Targeted PEGylated Gene Carrier, Characterization of Its Complex with DNA, and Transfection of Hepatoma Cells, Bioconjugate Chem., 2004, 15: 754-764
[36]汪长华,大豆磷脂脂质体的简易超声制备,湖北省职工医学院学报,1995, 2: 41-43
[1] Zhang W. J., Biotechnology of Complex Polysaccharide, 2nd ed., Zhejiang University Press, Hangzhou, 1987 (in Chinese)
[2] Varski A., Biological roles of oligosaccharides: all of the theories are correct, Glycobiology, 1993, 3: 97-130
[3] Bertozzi C. R., Kiessling L. L., Chemical Glycobiology, Science, 2001, 291(5512): 2357-2364
[4] Sears P., Wong C. H., Enzyme action in glycoprotein synthesis, Cell. Mol. Life Sci., 1998, 54: 243-252
[5] Chittaboina S., Xie F., Wang Q. et al, One-pot synthesis of triazole-linked glycoconjugates, Tetrahedron Lett., 2005, 46(13): 2331-2336
[6] Matile S., Berova N., Nakanishi K. et al, Porphyrins: Powerful Chromophores for Structural Studies by Exciton-Coupling Circular Dichroism, J. Am. Chem. Soc., 1995, 117(26): 7021-7022
[7] Jiménez C., Riguera R., Phenylethanoid glycosides in plants: structure and biological activity, Nat. Prod. Rep., 1994, 11 (6): 591-606
[8]尚遂存,兰淑琴等,中草药食品抗氧化荆的筛选,天然产物研究与开发,1994, 6(1): 36-38
[9] Lee L. V., Mitchell M. L., Huang S. J. et al, A Potent and Highly Selective Inhibitor of Humanα-1,3-Fucosyltransferasevia Click Chemistry, J. Am. Chem. Soc., 2003, 125(32): 9588-9589
[10] Wilkinson B. L., Bornaghi L. F., Houston T. A. et al, Carbonic Anhydrase Inhibitors: Inhibition of Isozymes I, II, and IX with Triazole-Linked O-Glycosides of Benzene Sulfonamides, J. Med. Chem., 2007, 50(7): 1651-1657
[11] Asano N., Glycosidase inhibitors: update and perspectives on practical use, Glycobiology, 2003, 13(10): 93R-104R
[12] Jean M. H., Elsen V. D., Kuntz D. A. et al, Structure of Golgiα-mannosidase II: a target for inhibition of growth and metastasis of cancer cells, The EMBO Journal, 2001, 20(12): 3008-3017
[13] Rossi L. L., Basu A., Glycosidase inhibition by 1-glycosyl-4-phenyl triazoles, Bioorg. Med. Chem. Lett., 2005, 15: 3596-3599
[14] Wang J., Uttamchandani M., Li J. Q. et al, Rapid Assembly of Matrix Metalloprotease Inhibitors Using Click Chemistry, Org. Lett., 2006, 8(17): 3821-3824
[15] Gordon E. J., Sanders W. J., Kiessling L. L., Synthetic ligands effect cell surface strategies, Nature, 1998, 392: 30-31
[16] Kitov P. I., Sadowska J. M., Mulvey G. et al, Shiga-like toxins neutralized by tailored multivalent carbohydrate ligands, Nature, 2000, 403: 669-672
[17] Bovin N. V., Gabius H. J., Polymer-immobilized carbohydrate ligands: versatile chemical tools for biochemistry and medical sciences, Chem. Soc. Rev., 1995, 24: 413-421
[18] Paulsen H., Advances in Selective Chemical Syntheses of Complex Oligosaccharides, Angew. Chem. Int. Ed. Engl., 1982, 21, 155-173
[19] Chang G. X., Lowary T. L., A Glycosylation Protocol Based on Activation of Glycosyl 2-Pyridyl Sulfones with Samarium Triflate, Org. Lett., 2000, 2(11): 1505-1508
[20] Yamago S., Yamada T., Hara O. et al, A New Iterative Strategy of Oligosaccharide Synthesis Based on Highly Reactiveβ-Bromoglycosides Derived from Selenoglycosides, Org. Lett., 2001, 3(24): 3867-3870
[21] Friesen R. W., Danishefsky S. J., On the controlled oxidative coupling of glycals: a new strategy for the rapid assembly of oligosaccharides, J. Am. Chem. Soc.,1989, 111(17): 6656-6660
[22] Zhu T., Boons G. J., Thioglycosides Protected as Trans-2,3-Cyclic Carbonates in Chemoselective Glycosylations, Org. Lett., 2001, 3(26): 4201-4203
[23] Fridman M., Solomon D., Yogev S. et al, One-Pot Synthesis of Glucosamine Oligosaccharides, Org. Lett., 2002, 4(2): 281-283
[24] Tanaka H., Adachi M., Tsukamoto H. et al, Synthesis of Di-Branched Heptasaccharide by One-Pot Glycosylation Using Seven Independent Building Blocks, Org. Lett., 2002, 4(24): 4213-4216
[25] Raghavan S., Kahne D., A one step synthesis of the ciclamycin trisaccharide, J. Am. Chem. Soc., 1993, 115(4): 1580-1581
[26] Fan W. Q., Katritzky A. R., Comprehensive Heterocyclic Chemistry II, Katritzky A. R., Rees C. W., Scriven E. F. V. E., Elsevier Science: Oxford, 1996, 4: 1-126
[27] Mishra R. M., Tewari N., Verma S. S. et al, 1,3-Dipolar Cycloaddition of Glycosyl Nitrile Oxides with Alkenes: Diastereoselective Synthesis of Glycosyl Isoxazolines, J. Carbohydr. Chem., 2004, 23: 353-374
[28] Perez-Balderas F., Hernandez-Mateo F., Santoyo-Gonzalez F., Synthesis of multivalent neoglycoconjugates by 1,3-dipolar cycloaddition of nitrile oxides and alkynes and evaluation of their lectin-binding affinities, Tetrahedron, 2005, 61: 9338-9348
[29] Rostovtsev V. V., Green L. G., Fokin V. V. et al, A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective“Ligation”of Azides and Terminal Alkynes, Angew. Chem. Int. Ed., 2002, 41(14): 2596-2599
[30] Kolb H. C., Finn M. G., Sharpless K. B. et al, Click Chemistry: Diverse Chemical Function from a Few Good Reactions, Angew. Chem. Int. Ed., 2001, 40(11): 2004-2021
[31] Torn?e C.W., Christensen C., Meldal M. et al, Peptidotriazoles on Solid Phase: [1,2,3]-Triazolesby Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides, J. Org. Chem., 2002, 67(9): 3057-3064
[32] Kuijpers B. H. M., Groothuys S., Keereweer A. R. et al, Expedient Synthesis of Triazole-Linked Glycosyl Amino Acids and Peptides, Org. Lett., 2004, 6(18): 3123-3126
[33] Billing J. F., Nilsson U. J., C2-Symmetric Macrocyclic Carbohydrate/Amino Acid Hybrids through Copper(I)-Catalyzed Formation of 1,2,3-Triazoles, J. Org. Chem., 2005, 70(12): 4847-4850
[34] Dondoni A., Giovanninni P. P., Massi A. et al, Assembling Heterocycle-Tethered C-Glycosyl and -Amino Acid Residues via 1,3-Dipolar Cycloaddition Reactions, Org. Lett., 2004, 6(17): 2929-2932.
[35] Chittaboina S., Xie F., Wang Q. et al, One-pot synthesis of triazole-linked glycoconjugates, Tetrahedron Lett., 2005, 46(13): 2331-2336
[36] Hotha S., Anegundi R. I., Natu A. A. et al, Expedient synthesis of 1,2,3-triazole-fused tetracyclic compounds by intramolecular Huisgen (‘click’) reactions on carbohydrate-derived azido-alkynes, Tetrahedron Lett., 2005, 46(27): 4585-4588
[37] Joosten J. A. F., Tholen N. T. H., Maate F. A. E. et al, High yielding microwave assisted synthesis of triazole-linked glycodendrimers via copper catalyzed [3+2] cycloaddition, Eur. J. Org. Chem., 2005: 3182-3185
[38] Ermolat'ev D., Dehaen W., Eycken Vd. E., Indirect Coupling of the 2(1H)-pyrazinone Scaffold with Various (oligo)-saccharides via“click chemistry”: en route towards Glycopeptidomimetics, QSAR & Comb. Sci., 2004, 23(10): 915-918
[39] Salameh B. A., Leffler H., Nilsson U. F., Thioureido N-acetyllactosamine derivatives as potent Galectin-7 and 9N Inhibitors, Bioorg. Med. Chem. Lett., 2005, 15: 3344-3346
[40] Wilkinson B. L., Bornaghi L. F., Poulsen S. A. et al, Synthetic utility of glycosyl triazoles in carbohydrate chemistry, Tetrahedron, 2006, 62(34): 8115-8125
[41] Hotha S., Kashyap S.,“Click Chemistry”Inspired Synthesis of pseudo-Oligosaccharides and Amino Acid Glycoconjugates, J. Org. Chem., 2006, 71(1): 364-367
[42] Dalvie D. K., Kalgutkar A. S., Bakht K. et al, Biotransformation Reactions of Five-Membered Aromatic Heterocyclic Rings, Chem. Res. Toxicol., 2002, 15: 269-299
[43] Horne W. S., Yadav M. K., Stou C. D. et al, Heterocyclic Peptide Backbone Modifications in an -Helical Coiled Coil, J. Am. Chem. Soc., 2004, 126 (47): 15366-15367
[44] Fazio F., Bryan M. C., Blixt O. et al, Synthesis of Sugar Arrays in Microtiter Plate, J. Am. Chem. Soc., 2002, 124(48): 14397-14402
[45] Wang Q., Chan T., Hilgraf R. et al, Bioconjugation by Copper(I)-Catalyzed Azide-Alkyne [3 + 2]Cycloaddition, J. Am. Chem. Soc., 2003, 125(11): 3192-3193
[46] Speers A. E., Adam G. C., Cravatt B. F., Activity-Based Protein Profiling in Vivo Using a Copper(I)-Catalyzed Azide-Alkyne [3+2] Cycloaddition, J. Am. Chem. Soc., 2003, 125(16): 4686-4687
[47] Seo T. S., Li Z., Ruparel H. et al, Click Chemistry to Construct Fluorescent Oligonucleotides for DNA Sequencing, J. Org. Chem., 2003, 68(2): 609-612
[48] Link A. J., Tirrell D. A., Cell Surface Labeling of Escherichia coli via Copper(I)-Catalyzed [3+2] Cycloaddition, J. Am. Chem. Soc., 2003, 125(37): 11164-11165
[49] Deiters A., Cropp T. A., Mukherji M. et al, Adding Amino Acids with Novel Reactivity to the Genetic Code of Saccharomyces Cerevisiae, J. Am. Chem. Soc., 2003, 125(39):11782-11783
[50] Sivakumar K., Xie F., Cash B. et al, A Fluorogenic 1,3-Dipolar Cycloaddition Reaction of 3-Azidocoumarins and Acetylenes, Org. Lett., 2004, 6(24): 4603-4606
[51] Zhan W., Barnhill H. N., Sivakumar K. et al, Synthesis of hemicyanine dyes for‘click’bioconjugation, Tetrahedron Lett., 2005, 46(10): 1691-1695
[52] Rabenau A., The role of hydrothermal synthesis in preparative chemistry, Angew. Chem. Int. Ed. Engl., 1985, 24: 1026-1040
[53] Byrappa K., Masahiro Y., Handbook of Hydrothermal Technology: A Technology for Crystal Growth and Materials Processing, New York: William Andrew Publishing, 2001
[54] Feng P. Y., Bu X. H., Stucky G. D., Hydrothermal syntheses and structural characterization of zeolite analogue compounds based on cobalt phosphate, Nature, 1997, 388(6644): 735-741
[55] Ducray R., Ciufolini M. A., Total Synthesis of (±) FR66979, Angew. Chem.Int. Ed., 2002, 41(24): 4688-4691
[56] Kim S., Lee Y. M., Lee J. et al, Expedient Syntheses of Antofine and Cryptopleurine via Intramolecular 1,3-Dipolar Cycloaddition, J. Org. Chem., 2007, 72: 4886-4891
[57] Schultz A. G., Dittami J. P., Myong S. O., A New 2-Azatricyclo[4 .4.0.02,8]decenonSe ynthesis and Ketene Formation by Retro-Diels-Alder Reaction, J. Am. Chem. Soc., 1983, 105: 3273-3219
[58] Sheldrick G. M. SADABS, Program for Empirical Absorption Correction of Area Detector Data, University of Gottingen, Germany, 1996
[59] Sheldrick G. M., SHELXTL V5.1, Software Reference Manual, Bruker AXS, Inc., Madison, Wisconsin, USA, 1997
[60] Wilson A. J., International Table for X-ray Crystallography, Vol. C, Kluwer AcademicPublishers, 1992, Dordrecht: Tables 6.1.1.4 (pp.500-502) and 4.2.6.8 (pp.219-222) respectively
[2]俞飙,金城,糖的化学和生物科学,21世纪有机化学发展战略,杜灿屏,刘鲁生,张恒主编,第一版,北京,化学工业出版社,2002: 298-306
[3] Haltiwanger R. S., Lowe J. B., Role of glycosylation in development, Annu. Rev. Biochem., 2004, 73: 491-537
[4] Cobb B. A., Wang Q., Tzianabos A. O. et al, Polysaccharide processing and presentation by the MHCII pathway, Cell, 2004, 117: 677-687
[5] Adeoye O. M., Ferrell R. E., Kirshner M. A. et al, 1-Acid Glycoprotein in Late-Life Depression: Relationship to Medical Burden and Genetics, J. Geriatr Psychiatry Neurol., 2003, 16(4): 235-239
[6] Swingler S., Brichacek B., Jacque J. M. et al, HIV-I Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection, Nature, 2003, 424: 213-219
[7] Kim H. M., Kim L. J., Danishefsky S. J., Total Syntheses of Tumor-Related Antigens N3: Probing the Feasibility Limits of the Glycal Assembly Method, J. Am. Chem. Soc., 2001, 123(1): 35-48
[8] Kolter T., Sandhoff K., Sphingolipids-their Metabolic Pathways and the Pathobiochemistry of Neurodegenerative Diseases, Angew. Chem. Int. Ed., 1999, 38(11): 1532-1568
[9] Rademacher T. W., Parekh R. B., Dwek R. A., Glycobiology, Annu. Rev. Biochem., 1988, 57: 785-838
[10] Lemieux R. U., The origin of the specificity in the recognition of oligosaccharides by proteins, Chem. Soc. Rev., 1989, 18: 347-374
[11] Kunz H., Glyciopeptides of biological interest: A challenge for chemical synthsis, Pure&Appl. Chem., 1993, 65(6): 1223-1232
[12] Zhao N., Kumar N., Neuenschwander K. et al, Quaternary Ammonium Salts as Chromophores for Exciton-Coupled Circular Dichroism: Absolute Configuration of Hypocholesterolemic Quinuclidines, J. Am. Chem. Soc., 1995, 117(29): 7844-7845
[13] Matile S., Berova N., Nakanishi K. et al, Porphyrins: Powerful Chromophores for Structural Studies by Exciton-Coupled Circular Dichroism, J. Am. Chem. Soc., 1995, 117(26): 7021-7022
[14]尚遂存,兰淑琴等,中草药食品抗氧化荆的筛选,天然产物研究与开发,1994, 6(1): 36-38
[15] Lee L. V., Mitchell M. L., Huang S. J. et al, A Potent and Highly Selective Inhibitor of Human
[16] Wilkinson B. L., Bornaghi L. F., Houston T. A. et al, Carbonic Anhydrase Inhibitors: Inhibition of Isozymes I, II, and IX with Triazole-Linked O-Glycosides of Benzene Sulfonamides, J. Med. Chem., 2007, 50(7): 1651-1657
[17] Asano N., Glycosidase inhibitors: update and perspectives on practical use, Glycobiology, 2003, 13(10): 93R-104R
[18] Jean M. H., Elsen V. D. , Kuntz D. A. et al, Structure of Golgiα-mannosidase II: a target for inhibition of growth and metastasis of cancer cells, The EMBO Journal, 2001, 20(12): 3008-3017
[19] Rossi L. L., Basu A., Glycosidase inhibition by 1-glycosyl-4-phenyl triazoles, Bioorg. Med. Chem. Lett., 2005, 15: 3596-3599
[20] Wang J., Uttamchandani M., Li J. Q. et al, Rapid Assembly of Matrix Metalloprotease Inhibitors Using Click Chemistry, Org. Lett., 2006, 8(17): 3821-3824
[21] Bertozzi C. R., Kiessling L. L., Carbohydrates and Glycobiology-Chemical Glycobiology, Science, 2001, 291(23): 2357-2364
[22] Davis B. G., Recent developments in glycoconjugate, J. Chem. Soc. Perkin Trans. 1, 1999: 3215-3237
[23] Bezou?ka K., Design functional evaluation and Biomedical applications of carbohydrate dendrimers (glycodendrimers), Rev. Mole. Biotech., 2002, 90: 269-290
[24] Mammen M., Choi S. K., Whitesides G. M., Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors, Angew. Chem. Int. Ed., 1998, 37: 2754-2794
[25] Patri A. K., Kukowska-Latallo J. F., Baker J. R., Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion comples, Adv. Drug Deliv. Rev., 2005, 57: 2203-2214
[26] Arcadio C., Pieter R. C., Recent advances in liposome technologies and their applications for systemic gene delivery, Adv. Drug Deliv. Rev., 1998, 30: 73-83
[27] Jain A. K., Panchagnula R., Skeletal drug delivery systems, Int. J. Pharm., 2000, 206: 1-12
[28] Spiess M., The Asialoglycoprotein Receptor: A Model for Endocytic Transport Receptors, Biochemistry, 1990, 29(43): 10009-10018
[29] Drickamer K., Biology of animal lectins, Annu. Rev. Cell Biol., 1993, 9: 237-264
[30] Meier M., Bider M. D., Malasherkevich V. N. et al, Crystal structure of the carbohudrate recognition domain of the H1 subunite of the asialoglycoprotein receptor, J. Mol. Biol., 2000, 300: 857-865
[31] Bider M. D., Spiess M., Ligand-induced endocytosis of the asialoglycoprotein receptor: evidencefor heterogeneity in subunit oligomerization, FEBS Lett., 1998: 37-41
[32] Vera D. R., Stadalnik R. C., Krohn K. A., Technetium-99m galactosylneoglycoalbumin: preparation and preclinical studies, J. Nucl. Med., 1985, 26(10): 1157-1167
[33] Nishikawa M., Kamijo A., Fujita T. et al, Synthesiss and pharmacokinetics of a new liver-specific carrier, glycosylated Carboxymethyl-Dextran, and its application to drug targeting , Pharma Res., 1993, 10(9): 1253-1261
[34] Goto M., Yura H., Chang C. W. et al, Lactose-carrying polystyrene as a drug carrier: investigation of body distrubutions to parenchymal liver cells using 125I-labelled lactose carrying polystyrene, J. Controlled Release, 1994, 28(1-3): 223-233
[35]管昌田,钟裕国,梁正路等,糖基干扰素的合成及其肝靶向性的研究,中华核医学杂志,1996, 16 (I): 58-59
[36] Nishikawa M., Miyazaki C., Yamashita F. et al, Galactosylated proteins are recognized by the liver according to the surface density of galactose moieties, Am. J. Physiol., 1995, 268: 6849-6856
[37]梁正路,付辛,管昌田等,双糖密度半乳糖基胰岛素的合成及肝靶向性初步研究,华西医大学报,2000, 31(1): 1-4
[38] Zhang X., Simmons C. G., Corey D. R., Liver cell specific targeting of peptide nucleic acid oligomers, Bioorg. Med. Chem. Lett., 2001, 11(10): 1269-1272
[39] Kawakami S., Munakata C., Funotos S. et al, Targeted delivery of prostaglandin EI to hepatocytes using galactosylated liposomes, J. Drug Target, 2000, 8(3): 137-142
[40] Kawakami S., Yamashita F., Nishikawa M. et al, Asialoglycoprotein receptor-mediated gene transfer using novel galactosylated cationic liposomes, Biochem. Biophys. Res. Commun., 1998, 252: 78-83
[41]海俐,无唾液酸糖蛋白受体介导的肝靶向脂质体配体的设计、合成及靶向性研究,四川大学,2006
[42] Rensen P. C. N., Sliedregt L. A. J. M., Perns M. et al, Determination of the upper size limit for uptake and processing of ligands by the asialoglycoprotein receptor on hepatocytes in vitro and in vivo, J. Biochem. Chem., 2001, 276(40): 37577-37584
[43] Sliedregt L. A. J. M., Rensen P. C. N., Rump E. T. et al, Design and synthesis of novel amphiphilic dendritic galactosides for selective targeting of liposomes to the hepatic asialoglycoprotein receptor, J. Med. Chem., 1999, 42(4): 609-618
[44] Rensen P. C. N., Leeuwen S. H. V., Sliedregt L. A. J. M. et al, Design and Synthesis of Novel N-Acetylgalactosamine-Terminated Glycolipids for Targeting of Lipoproteins to the Hepatic Asialoglycoprotein Receptor, J. Med. Chem., 2004, 47(23): 5798-5808
[45] Rensen P. C. N., Sliedregt L. A. J. M., Santbrink P. J. V., Stimulation of Liver-Directed Cholesterol Flux in Mice by Novel N-Acetylgalactosamine-Terminated Glycolipids with High Affinity for the Asialoglycoprotein Receptor, Arterioscler. Thromb. Vasc. Biol., 2006, 26: 169-175
[46] Lee Y. C., Townsend R. R., Hardy M. R. et al, Binding of synthetic oligosaccharides to the hepatic Gal/GalNAc lectin. Dependence on fine structural features, J. Biol. Chem., 1983, 258: 199-202
[47] Biessen E. A. L., Beuting D. M., Roelen H. C. P. F. et al, Synthesis of Cluster Galactosides with High Affinity for the Hepatic Asialoglycoprotein Receptor, J. Med. Chem., 1995, 38(9): 1538-1546
[48] Sliedregt L. A. J. M., van Rossenberg S. M. W., Autar R. et al, Design and synthesis of a multivalent homing device for targeting to murine CD22, Bioorg. Med. Chem., 2001, 9(1): 85-97
[49] Ren T., Zhang G., Liu D., Synthesis of galactosyl compounds for targeted gene delivery, Bioorg. Med. Chem., 2001, 9: 2969-2978
[50] Iobst S. T., Drickamer K., Selective Sugar Binding to the Carbohydrate Recognition Domains of the Rat Hepatic and Macrophage Asialoglycoprotein Receptors, J. Biol. Chem., 1996, 271: 6686-6693
[51]王葆仁,有机合成反应(上册),北京:科学出版社,1982: 418-452
[52] Huisgen R., Mechanism of 1,3-dipolar cycloadditions, J. Org. Chem., 1968, 33(6): 2291-2297
[53] Kolb H. C., Finn M. G., Sharpless K. B., Click Chemistry: Diverse Chemical Function from a Few Good Reactions. Angew. Chem. Int. Ed., 2001, 40: 2004-2021
[54]李娟,段明,张烈辉等,点击化学及其应用,化学进展,2007, 19 (11): 1754-1760
[55] Patton G. C., Development and Applications of Click Chemistry, [2006-12-11]. http://forum.e2002. com/read.php? tid=78386&fpage=0 &toread=&page=1
[56] Franke R., Doll C., Eichler J., Peptide ligation through click chemistry for the generation of assembled and scaffolded peptides, Tetrahedron Lett., 2005, 46: 4479-4482
[57] Rossi L. L., Basu A., Glycosidase inhibition by 1-glycosyl-4-phenyl triazoles, Bioorg. Med. Chem. Lett., 2005, 15: 3596-3599
[58] Pérez-Balderas P., Ortega-Muňoz M., Santoyo-González F., et al. Multivalent Neoglyco- conjugates by Regiospecific Cycloaddition of Alkynes and Azides Using Organic-Soluble Copper Catalysts, Org. Lett., 2003, 5: 1951-1954
[59] Arosio D., Bertoli M., Manzoni L. et al, Click chemistry to functionalise peptidomimetics, Tetrahedron Lett., 2006, 47: 3697-3700
[60] Radic Z., Manetsch R., Sharpless K. B. et al, Molecular basis of interactions of cholinesteraseswith tight binding inhibitors, Chemico-Biological Interactions, 2005, 157/158: 133-141
[61] Manetsch R., Krasiński A., Radic Z. et al, In Situ Click Chemistry: Enzyme Inhibitors Made to Their Own Specifications, J. Am. Chem. Soc., 2004, 126: 12809-12018
[62] Weber L., Drug Discovery Today, 2004, 1: 261-267
[63] Speers A. E., Adam G. C., Cravatt B. F, Activity-Based Protein Profiling in Vivo Using a Copper(I)-Catalyzed Azide-Alkyne [3+2] Cycloaddition, J. Am. Chem. Soc., 2003, 125: 4686-4687
[64] Speers A. E., Cravatt B. F., Profiling Enzyme Activities In Vivo Using Click Chemistry Methods, Chem. Biol., 2004, 11: 535-546
[65] Gao H. F., Matyjaszewski F., Synthesis of Star Polymers by a Combination of ATRP and the "Click" Coupling Method, Macromolecules, 2006, 39: 4960-4965
[66] Ossipov D. A., Hilborn J., Poly(vinyl alcohol)-Based Hydrogels Formed by "Click Chemistry", Macromolecules, 2006, 39: 1709-1718
[67] Vogt A. P., Sumerlin B. S., An Efficient Route to Macromonomers via ATRP and Click Chemistry, Macromolecules, 2006, 39: 5286-5292
[68] Liu Q. C., Chen Y. M., Synthesis of well-defined macromonomers by the combination of atom transfer radical polymerization and a click reaction, J. Polym. Sci., Part A: Polym. Chem., 2006, 44: 6103-6113
[69] Lee J. W., Kim J. H., Jin S. H. et al, Synthesis of Fréchet type dendritic benzyl propargyl ether and Fréchet type triazole dendrimer, Tetrahedron, 2006, 62: 894-900
[70] Li H. M., Cheng F. Y., Adronov A., Functionalization of Single-Walled Carbon Nanotubes with Well-Defined Polystyrene by "Click" Coupling, J. Am. Chem. Soc., 2005, 127: 14518- 14524
[71] Oreilly R. K., Joralemon M. J., Hawker C. J. et al, Facile Syntheses of Surface-functionalized Micelles and Shell Cross-linked Nanoparticles, J. Polym. Sci., Part A: Polym. Chem., 2006, 44: 5203-5217
[72] Such G. K., Quinn J. F., Caruso F. et al, Assembly of Ultrathin Polymer Multilayer Films by Click Chemistry, J. Am. Chem. Soc., 2006, 128: 9318-9319
[73] Diaz D. D., Fokin V. V., Sharpless K. B. et al, chemistry in materials synthesis. 1. Adhesive polymers from copper-catalyzed azide-alkyne cycloaddition, J. Polym. Sci., Part A: Polym. Chem., 2004, 42: 4392-4403
[74] Slater M., Snauko M., Svec F., Frechet J. M. J., "Click Chemistry" in the Preparation of Porous Polymer-Based Particulate Stationary Phases forμ-HPLC Separation of Peptides and Proteins, Anal. Chem., 2006; 78(14): 4969-4975
[1] Hashida M., Nishikawa M., Takakura Y. J., Hepatic targeting of drugs and proteins by chemical modification, Controlled Release, 1995, 36: 99-107
[2] Gestwicki J. E., Cairo C. W., Strong L. E., Influencing Receptor-Ligand Binding Mechanisms with Multivalent Ligand Architecture, J. Am. Chem. Soc., 2002, 124(50): 14922-14933
[3] Frisch B., Carrière M., Largeau C. et al, A New Triantennary Galactose-Targeted PEGylated Gene Carrier, Characterization of Its Complex with DNA and Transfection of Hepatoma Cells, Bioconjugate Chem., 2004, 15: 754-764
[4] Sharma A., Sharma U. S., Liposomes in drug delivery: progress and limitations, Inter. J. Pharma., 1997, 154: 123-140
[5] Harashima H., Kiwada H., Liposomal targeting and drug delivery: kinetic consideration, Adv. Drug Delivery Rev., 1996, 19: 425-444
[6] Davis B. G., Recent developments in glycoconjugate, J. Chem. Soc., Perkin Trans. 1, 1999: 3215-3237
[7] Bezou?ka K., Design functional evaluation and Biomedical applications of carbohydrate dendrimers (glycol-dendrimers), Reviews in Molecular Biotech., 2002, 90: 269-290
[8] Rensen P. C. N., Sliedregt L. A. J. M., Ferns M. et al, Determination of the Upper Size Limit for Uptake and Processing of Ligands by the Asialoglycoprotein Receptor on Hepatocytes in Vitro and in Vivo, J Bio. Chem., 2001, 276(40): 37577-37584
[9] Langer P., Ince S. J., Ley S. V., Assembly of dendritic glycocluster from monomeric mannose building blocks, J. Chem. Soc., Perkin Trans 1, 1998, 23: 3913-3915
[10] Zanini D., Roy R., Novel Dendriticα-Sialosides: Synthesis of Glycodendrimers Based on a 3,3’-Iminobis (propylamine) Core, J. Org. Chem., 1996, 61: 7348-7354
[11] Ashton P. R., Boyd S. E., Stoddart J. F. et al, Synthesis of Glycodendrimers by Modification of Poly(propylene imine) Dendrimers, Chem. Eur. J., 1997, 6: 974-984
[12] Roy R., Saha U. K., Rational design of multivalent glycoconjugate ligands and synthesis of libraries of conformationally flexible rotamers of poly-N-linked lactosyl glycines, Chem. Commun., 1996, 2: 201-202
[13]孔繁祚,糖化学,主编朱清时,北京:科学出版社,2005: 342-343.
[14] Kiessling L. L., Gestwicki J. E., Strong L. E., On the hepatocellular surface in mice lacking theminor receptor subunit, Curr. Opin. Chem. Biol., 2000, 4: 696-703
[15] Brian S., Furniss, Antony J. et al, Vogel′s Textbook of Practical Organic Chemistry, Fifth Edition, London: Longman Science & Technical World Publishing Corp, 1989: 875
[16] Zhang X. R., Li Y. X., Chu S. D., et al, Synthesis of Glutamic Acid-based Cluster Galactosides and Their Binding Affinities with Liver Cells, Chin. J. Chem., 2004, 22: 482-486
[17] Lee R. T., Lee Y. C., Facile Synthesis of a High-Affinity Ligand for Mammalian Hepatic Lectin Containing Three Terminal N-Acetylgalactosamine Residues, Bioconjugate Chem., 1997, 8: 762-765
[18] Wang S. N., Deng Y. H., Xu H. et al, Synthesis of a novel galactosylated lipid and its application to the hepatocyte-selective targeting of liposomal doxorubicin, Eur. J. Pharma. Biopharm., 2006, 62: 32-38
[19] Chwarfz H., Bumpus F. M., Page I. H., Synthesis of a Biologically Active Octapeptide Similar to Natural Isoleucine Angiotonin Octapeptide, J. Am. Chem. Soc., 1957, 5: 5697-5703
[20] Hanby W. E., Waley S. G., Watson J., Synthetic Polypeptides. Part II. Polyglutamic Acid, J. Am. Chem. Soc., 1950, 632: 3239-3249
[21] Jorba X., Gill I., Vulfson E. N., Enzymatic Synthesis of the Delicious Peptide Fragments in Eutectic Mixtures, J. Agric. Food Chem., 1995, 43: 2536-2541
[22] Rodriguez M., Fulcrand P., Laur J. et al, Synthesis of Gastrin Antagonists, Analogues of the C-Terminal Tetrapeptide of Gastrin, by Introduction of aβ-Homo Residue, J. Med. Chem., 1989, 32: 522-528
[1]潘国宗主编,现代胃肠病学,北京,科技出版社,1998: 504-514
[2] Andrea T., Christian W., Genes involved in hepatocellular carcinoma: deregulation in cell cycling and apoptosis, Virchows Arch., 2002, 440: 345-352
[3] Poon R. T., Fan S. T., Tsang F. H. et al, Locoregional therapies hepatocellular carcinoma: cricital review from the surgeon's perspective, Ann. Surg., 2002, 235(4): 466-486
[4] Dizon D. S., Kemeny N. E., Intrahepatic arterial infusion of chemotheraphy: clinical results, Semin. Oncol., 2002, 29(2): 126-135
[5]叶胜龙,肝癌的非手术治疗,现代肿瘤医学杂志,1994, 3 (2): 129-130
[6] http://www.avantilipids.com/Liposomes.asp
[7] Crommclin D. J. A., Liposomes as carries for drugs and antigens approaches to preserve their long term stability, Drugs Dev. Pharm., 1994, 20(4): 540-551
[8] Harashima H., Kiwada H., Liposomal targeting and drug delivery: kinetic consideration, Adv. Drug Delivery Rev., 1996, 19: 425-444
[9] Sharma A., Sharma U. S., Liposomes in drug delivery: progress and limitations, Inter. J. Pharma., 1997, 154: 123-140
[10] Hashida M., Akamatsu K., Nishikava M. et al, Design of polymeric prodrugs of prostaglandin E-1 having galactose residue for hepatocyte targeting, J. Controlled Release, 1999, 62: 253-262
[11] Vrueh R. L. A., Rump E. T., Bilt E. V. et al, Carrier-mediated delivery of 9-(2-phosphonyl- methoxyethyl) adenine to parenchymal liver cells: A novel therapeutic approach for hepatitis B, Antimicrob. Agents Chemother., 2000, 44: 477-483
[12] Cho C. S., Cho K. Y., Park I. J. et al, Receptor-mediated delivery of all transretinoic acid to hepatocyte using poly(L-lactic acid) nanoparticles coated with galactose-carrying polystyrene, J. Controlled Release, 2001, 77: 7-15
[13] Kassab R., Parrot-Lopez H., Fessi H. et al, Molecular recognition by Kluyveromyces of amphotericin-loaded, galactose-tagged, poly (lactic acid) microspheres, Bioorg. Med. Chem., 2002, 10: 1767-1775
[14] Ishida E., Managit C., Kawakami S. et al, Biodistribution characteristics of galactosylated emulsions and incorporated probucol for hepatocyte-selective targeting of lipophilic drugs in mice, Pharm. Res., 2004, 21: 932-939
[15] Nag A., Ghosh P. C., Assessment of targeting potential of galactosylated and mannosylatedsterically stabilized liposomes to different cell types of mouse liver, J. Drug Target., 1999, 6: 427-438
[16] Kawakami S., Wong J., Sato A., Hattori Y. et al, Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice, Biochim. Biophys. Acta., 2000, 1524: 258-265
[17] Hassane F. S., Frisch B., Schuber F., Targeted Liposomes: Convenient Coupling of Ligands to Preformed Vesicles Using“Click Chemistry”, Bioconjugate Chem., 2006, 17: 849-854
[18] Gage M., Jain N. K., Reduced hematopoietic toxicity, enhanced cellular uptake and altered pharmacokinetics of azidothymidine loaded galactosylated liposomes, J. Drug Targeting, 2006, 14(1): 1-11
[19] Berna M., Dalzoppo D., Pasut G. et al, Novel Monodisperse PEG-Dendrons as New Tools for Targeted Drug Delivery: Synthesis, Characterization and Cellular Uptake, Biomacromolecules 2006, 7: 146-153
[20] Kawakami S., Munakata C., Fumoto S., Novel Galactosylated Liposomes for Hepatocyte- Selective Targeting of Lipophilic Drugs, J. Pharma. Sci., 2001, 90(2): 105-113
[21] Murao A., Nishikawa M., Managit C. et al, Targeting Efficiency of Galactosylated Liposomes to Hepatocytes in Vivo: Effect of Lipid Composition, Pharma. Res., 2002, 19(12): 1808-1814
[22] Managit C., Kawakami S., Yamashita F. et al, Effect of Galactose Density on Asialoglycoprotein Receptor-Mediated Uptake of Galactosylated Liposomes, J. Parma. Sci., 2005, 94(10): 2266-2275
[23] Ishida E., Managit C., Kawakami S. et al, Biodistribution characteristics of galactosylated emulsions and incorporated probucol for hepatocyte-selective targeting of lipophilic drugs in mice, Pharm. Res., 2004, 21: 932-939
[24] Kaiser N., Kimpfler A., Massing U. et al, 5-Fluorouracil in vesicular phospholipid gels for anticancer treatment: entrapment and release properties, Int. J. Pharm., 2003, 256: 123-131
[25] Mayer L. D., Tai L .C., Bally M. B. et al, Characterization of liposomal systems containing doxorubicin entrapped in response to pH gradients, Biochim. Biophys. Acta, 1990, 1025: 143-151
[26] Wang S. N., Deng Y. H., Xu H. et al, Synthesis of a novel galactosylated lipid and its application to the hepatocyte-selective targeting of liposomal doxorubicin, Eur. J. Pharma. Biopharm., 2006, 62: 32-38
[27] Sliedregt L. A. J. M., Rensen P. C. N., Rump E. T. et al, Design and Synthesis of Novel Amphiphilic Dendritic Galactosides for Selective Targeting of Liposomes to the Hepatic Asialoglycoprotein Receptor, J. Med. Chem., 1999, 42: 609-618
[28] Rensen P. C. N., Sliedregt L. A. J. M., Perns M. et al, Determination of the upper size limit for uptake and processing of ligands by the asialoglycoprotein receptor on hepatocytes in vitro and invivo, J. Biochem. Chem., 2001, 276(40): 37577-37584
[29] Rensen P. C. N., Leeuwen S. H. V., Sliedregt L. A. J. M. et al, Design and Synthesis of Novel N-Acetylgalactosamine-Terminated Glycolipids for Targeting of Lipoproteins to the Hepatic Asialoglycoprotein Receptor, J. Med. Chem., 2004, 47(23): 5798-5808
[30] Rensen P. C. N., Sliedregt L. A. J. M., Santbrink P. J. V. et al, Stimulation of Liver-Directed Cholesterol Flux in Mice by Novel N-Acetylgalactosamine-Terminated Glycolipids With High Affinity for the Asialoglycoprotein Receptor, Arterioscler. Thromb. Vasc. Biol., 2006, 26: 169-175
[31] Perouzel E., Jorgensen M. R., Keller M., Synthesis and Formulation of Neoglycolipids for the Functionalization of Liposomes and Lipoplexes, Bioconjugate Chem., 2003, 14: 884-898
[32] Merwin J. R., Noell G. S., Wendy L. et al, Targeted Delivery of DNA Using YEE(GalNAcAH)3, a Synthetic Glycopeptide Ligand for the Asialoglycoprotein Receptor, Bioconjugate Chem., 1994, 5: 612-620
[33] Singh M., Ariatti M., Targeted gene delivery into HepG2 cells using complexes containing DNA, cationized asialoorosomucoid and activated cationic liposomes, J. Controlled Release, 2003, 92: 383-394
[34] Kawakami S., Yamashita F., Nishikawa M. et al, Asialoglycoprotein Receptor-Mediated Gene Transfer Using Novel Galactosylated Cationic Liposomes, Biochem. Biophys. Res. Commu., 1998, 252(1): 78-83
[35] Frisch B., Carrière M., Largeau C. et al, A New Triantennary Galactose-Targeted PEGylated Gene Carrier, Characterization of Its Complex with DNA, and Transfection of Hepatoma Cells, Bioconjugate Chem., 2004, 15: 754-764
[36]汪长华,大豆磷脂脂质体的简易超声制备,湖北省职工医学院学报,1995, 2: 41-43
[1] Zhang W. J., Biotechnology of Complex Polysaccharide, 2nd ed., Zhejiang University Press, Hangzhou, 1987 (in Chinese)
[2] Varski A., Biological roles of oligosaccharides: all of the theories are correct, Glycobiology, 1993, 3: 97-130
[3] Bertozzi C. R., Kiessling L. L., Chemical Glycobiology, Science, 2001, 291(5512): 2357-2364
[4] Sears P., Wong C. H., Enzyme action in glycoprotein synthesis, Cell. Mol. Life Sci., 1998, 54: 243-252
[5] Chittaboina S., Xie F., Wang Q. et al, One-pot synthesis of triazole-linked glycoconjugates, Tetrahedron Lett., 2005, 46(13): 2331-2336
[6] Matile S., Berova N., Nakanishi K. et al, Porphyrins: Powerful Chromophores for Structural Studies by Exciton-Coupling Circular Dichroism, J. Am. Chem. Soc., 1995, 117(26): 7021-7022
[7] Jiménez C., Riguera R., Phenylethanoid glycosides in plants: structure and biological activity, Nat. Prod. Rep., 1994, 11 (6): 591-606
[8]尚遂存,兰淑琴等,中草药食品抗氧化荆的筛选,天然产物研究与开发,1994, 6(1): 36-38
[9] Lee L. V., Mitchell M. L., Huang S. J. et al, A Potent and Highly Selective Inhibitor of Humanα-1,3-Fucosyltransferasevia Click Chemistry, J. Am. Chem. Soc., 2003, 125(32): 9588-9589
[10] Wilkinson B. L., Bornaghi L. F., Houston T. A. et al, Carbonic Anhydrase Inhibitors: Inhibition of Isozymes I, II, and IX with Triazole-Linked O-Glycosides of Benzene Sulfonamides, J. Med. Chem., 2007, 50(7): 1651-1657
[11] Asano N., Glycosidase inhibitors: update and perspectives on practical use, Glycobiology, 2003, 13(10): 93R-104R
[12] Jean M. H., Elsen V. D., Kuntz D. A. et al, Structure of Golgiα-mannosidase II: a target for inhibition of growth and metastasis of cancer cells, The EMBO Journal, 2001, 20(12): 3008-3017
[13] Rossi L. L., Basu A., Glycosidase inhibition by 1-glycosyl-4-phenyl triazoles, Bioorg. Med. Chem. Lett., 2005, 15: 3596-3599
[14] Wang J., Uttamchandani M., Li J. Q. et al, Rapid Assembly of Matrix Metalloprotease Inhibitors Using Click Chemistry, Org. Lett., 2006, 8(17): 3821-3824
[15] Gordon E. J., Sanders W. J., Kiessling L. L., Synthetic ligands effect cell surface strategies, Nature, 1998, 392: 30-31
[16] Kitov P. I., Sadowska J. M., Mulvey G. et al, Shiga-like toxins neutralized by tailored multivalent carbohydrate ligands, Nature, 2000, 403: 669-672
[17] Bovin N. V., Gabius H. J., Polymer-immobilized carbohydrate ligands: versatile chemical tools for biochemistry and medical sciences, Chem. Soc. Rev., 1995, 24: 413-421
[18] Paulsen H., Advances in Selective Chemical Syntheses of Complex Oligosaccharides, Angew. Chem. Int. Ed. Engl., 1982, 21, 155-173
[19] Chang G. X., Lowary T. L., A Glycosylation Protocol Based on Activation of Glycosyl 2-Pyridyl Sulfones with Samarium Triflate, Org. Lett., 2000, 2(11): 1505-1508
[20] Yamago S., Yamada T., Hara O. et al, A New Iterative Strategy of Oligosaccharide Synthesis Based on Highly Reactiveβ-Bromoglycosides Derived from Selenoglycosides, Org. Lett., 2001, 3(24): 3867-3870
[21] Friesen R. W., Danishefsky S. J., On the controlled oxidative coupling of glycals: a new strategy for the rapid assembly of oligosaccharides, J. Am. Chem. Soc.,1989, 111(17): 6656-6660
[22] Zhu T., Boons G. J., Thioglycosides Protected as Trans-2,3-Cyclic Carbonates in Chemoselective Glycosylations, Org. Lett., 2001, 3(26): 4201-4203
[23] Fridman M., Solomon D., Yogev S. et al, One-Pot Synthesis of Glucosamine Oligosaccharides, Org. Lett., 2002, 4(2): 281-283
[24] Tanaka H., Adachi M., Tsukamoto H. et al, Synthesis of Di-Branched Heptasaccharide by One-Pot Glycosylation Using Seven Independent Building Blocks, Org. Lett., 2002, 4(24): 4213-4216
[25] Raghavan S., Kahne D., A one step synthesis of the ciclamycin trisaccharide, J. Am. Chem. Soc., 1993, 115(4): 1580-1581
[26] Fan W. Q., Katritzky A. R., Comprehensive Heterocyclic Chemistry II, Katritzky A. R., Rees C. W., Scriven E. F. V. E., Elsevier Science: Oxford, 1996, 4: 1-126
[27] Mishra R. M., Tewari N., Verma S. S. et al, 1,3-Dipolar Cycloaddition of Glycosyl Nitrile Oxides with Alkenes: Diastereoselective Synthesis of Glycosyl Isoxazolines, J. Carbohydr. Chem., 2004, 23: 353-374
[28] Perez-Balderas F., Hernandez-Mateo F., Santoyo-Gonzalez F., Synthesis of multivalent neoglycoconjugates by 1,3-dipolar cycloaddition of nitrile oxides and alkynes and evaluation of their lectin-binding affinities, Tetrahedron, 2005, 61: 9338-9348
[29] Rostovtsev V. V., Green L. G., Fokin V. V. et al, A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective“Ligation”of Azides and Terminal Alkynes, Angew. Chem. Int. Ed., 2002, 41(14): 2596-2599
[30] Kolb H. C., Finn M. G., Sharpless K. B. et al, Click Chemistry: Diverse Chemical Function from a Few Good Reactions, Angew. Chem. Int. Ed., 2001, 40(11): 2004-2021
[31] Torn?e C.W., Christensen C., Meldal M. et al, Peptidotriazoles on Solid Phase: [1,2,3]-Triazolesby Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides, J. Org. Chem., 2002, 67(9): 3057-3064
[32] Kuijpers B. H. M., Groothuys S., Keereweer A. R. et al, Expedient Synthesis of Triazole-Linked Glycosyl Amino Acids and Peptides, Org. Lett., 2004, 6(18): 3123-3126
[33] Billing J. F., Nilsson U. J., C2-Symmetric Macrocyclic Carbohydrate/Amino Acid Hybrids through Copper(I)-Catalyzed Formation of 1,2,3-Triazoles, J. Org. Chem., 2005, 70(12): 4847-4850
[34] Dondoni A., Giovanninni P. P., Massi A. et al, Assembling Heterocycle-Tethered C-Glycosyl and -Amino Acid Residues via 1,3-Dipolar Cycloaddition Reactions, Org. Lett., 2004, 6(17): 2929-2932.
[35] Chittaboina S., Xie F., Wang Q. et al, One-pot synthesis of triazole-linked glycoconjugates, Tetrahedron Lett., 2005, 46(13): 2331-2336
[36] Hotha S., Anegundi R. I., Natu A. A. et al, Expedient synthesis of 1,2,3-triazole-fused tetracyclic compounds by intramolecular Huisgen (‘click’) reactions on carbohydrate-derived azido-alkynes, Tetrahedron Lett., 2005, 46(27): 4585-4588
[37] Joosten J. A. F., Tholen N. T. H., Maate F. A. E. et al, High yielding microwave assisted synthesis of triazole-linked glycodendrimers via copper catalyzed [3+2] cycloaddition, Eur. J. Org. Chem., 2005: 3182-3185
[38] Ermolat'ev D., Dehaen W., Eycken Vd. E., Indirect Coupling of the 2(1H)-pyrazinone Scaffold with Various (oligo)-saccharides via“click chemistry”: en route towards Glycopeptidomimetics, QSAR & Comb. Sci., 2004, 23(10): 915-918
[39] Salameh B. A., Leffler H., Nilsson U. F., Thioureido N-acetyllactosamine derivatives as potent Galectin-7 and 9N Inhibitors, Bioorg. Med. Chem. Lett., 2005, 15: 3344-3346
[40] Wilkinson B. L., Bornaghi L. F., Poulsen S. A. et al, Synthetic utility of glycosyl triazoles in carbohydrate chemistry, Tetrahedron, 2006, 62(34): 8115-8125
[41] Hotha S., Kashyap S.,“Click Chemistry”Inspired Synthesis of pseudo-Oligosaccharides and Amino Acid Glycoconjugates, J. Org. Chem., 2006, 71(1): 364-367
[42] Dalvie D. K., Kalgutkar A. S., Bakht K. et al, Biotransformation Reactions of Five-Membered Aromatic Heterocyclic Rings, Chem. Res. Toxicol., 2002, 15: 269-299
[43] Horne W. S., Yadav M. K., Stou C. D. et al, Heterocyclic Peptide Backbone Modifications in an -Helical Coiled Coil, J. Am. Chem. Soc., 2004, 126 (47): 15366-15367
[44] Fazio F., Bryan M. C., Blixt O. et al, Synthesis of Sugar Arrays in Microtiter Plate, J. Am. Chem. Soc., 2002, 124(48): 14397-14402
[45] Wang Q., Chan T., Hilgraf R. et al, Bioconjugation by Copper(I)-Catalyzed Azide-Alkyne [3 + 2]Cycloaddition, J. Am. Chem. Soc., 2003, 125(11): 3192-3193
[46] Speers A. E., Adam G. C., Cravatt B. F., Activity-Based Protein Profiling in Vivo Using a Copper(I)-Catalyzed Azide-Alkyne [3+2] Cycloaddition, J. Am. Chem. Soc., 2003, 125(16): 4686-4687
[47] Seo T. S., Li Z., Ruparel H. et al, Click Chemistry to Construct Fluorescent Oligonucleotides for DNA Sequencing, J. Org. Chem., 2003, 68(2): 609-612
[48] Link A. J., Tirrell D. A., Cell Surface Labeling of Escherichia coli via Copper(I)-Catalyzed [3+2] Cycloaddition, J. Am. Chem. Soc., 2003, 125(37): 11164-11165
[49] Deiters A., Cropp T. A., Mukherji M. et al, Adding Amino Acids with Novel Reactivity to the Genetic Code of Saccharomyces Cerevisiae, J. Am. Chem. Soc., 2003, 125(39):11782-11783
[50] Sivakumar K., Xie F., Cash B. et al, A Fluorogenic 1,3-Dipolar Cycloaddition Reaction of 3-Azidocoumarins and Acetylenes, Org. Lett., 2004, 6(24): 4603-4606
[51] Zhan W., Barnhill H. N., Sivakumar K. et al, Synthesis of hemicyanine dyes for‘click’bioconjugation, Tetrahedron Lett., 2005, 46(10): 1691-1695
[52] Rabenau A., The role of hydrothermal synthesis in preparative chemistry, Angew. Chem. Int. Ed. Engl., 1985, 24: 1026-1040
[53] Byrappa K., Masahiro Y., Handbook of Hydrothermal Technology: A Technology for Crystal Growth and Materials Processing, New York: William Andrew Publishing, 2001
[54] Feng P. Y., Bu X. H., Stucky G. D., Hydrothermal syntheses and structural characterization of zeolite analogue compounds based on cobalt phosphate, Nature, 1997, 388(6644): 735-741
[55] Ducray R., Ciufolini M. A., Total Synthesis of (±) FR66979, Angew. Chem.Int. Ed., 2002, 41(24): 4688-4691
[56] Kim S., Lee Y. M., Lee J. et al, Expedient Syntheses of Antofine and Cryptopleurine via Intramolecular 1,3-Dipolar Cycloaddition, J. Org. Chem., 2007, 72: 4886-4891
[57] Schultz A. G., Dittami J. P., Myong S. O., A New 2-Azatricyclo[4 .4.0.02,8]decenonSe ynthesis and Ketene Formation by Retro-Diels-Alder Reaction, J. Am. Chem. Soc., 1983, 105: 3273-3219
[58] Sheldrick G. M. SADABS, Program for Empirical Absorption Correction of Area Detector Data, University of Gottingen, Germany, 1996
[59] Sheldrick G. M., SHELXTL V5.1, Software Reference Manual, Bruker AXS, Inc., Madison, Wisconsin, USA, 1997
[60] Wilson A. J., International Table for X-ray Crystallography, Vol. C, Kluwer AcademicPublishers, 1992, Dordrecht: Tables 6.1.1.4 (pp.500-502) and 4.2.6.8 (pp.219-222) respectively