Early Engineering Approaches to Improve Peptide Developability and Manufacturability
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- 作者：Jennifer L. Furman ; Mark Chiu ; Michael J. Hunter
- 关键词：developability ; peptide ; proteolysis ; PTM risk
- 刊名：The AAPS Journal
- 出版年：2015
- 出版时间：January 2015
- 年：2015
- 卷：17
- 期：1
- 页码：111-120
- 全文大小：1,364 KB
- 参考文献：1. Diao L, Meibohm B. Pharmacokinetics and pharmacokinetic-pharmacodynamic correlations of therapeutic peptides. Clin Pharmacokinet. 2013;52(10):855-8. lass="external" href="http://dx.doi.org/10.1007/s40262-013-0079-0" target="_blank" title="It opens in new window">CrossRef
2. Bruckdorfer T, Marder O, Albericio F. From production of peptides in milligram amounts for research to multi-tons quantities for drugs of the future. Curr Pharm Biotechnol. 2004;5(1):29-3. lass="external" href="http://dx.doi.org/10.2174/1389201043489620" target="_blank" title="It opens in new window">CrossRef
3. Vlieghe P / et al. Synthetic therapeutic peptides: science and market. Drug Discov Today. 2010;15(1-):40-6. lass="external" href="http://dx.doi.org/10.1016/j.drudis.2009.10.009" target="_blank" title="It opens in new window">CrossRef
4. Adessi C, Soto C. Converting a peptide into a drug: strategies to improve stability and bioavailability. Curr Med Chem. 2002;9(9):963-8. lass="external" href="http://dx.doi.org/10.2174/0929867024606731" target="_blank" title="It opens in new window">CrossRef
5. Witt KA / et al. Peptide drug modifications to enhance bioavailability and blood–brain barrier permeability. Peptides. 2001;22(12):2329-3. lass="external" href="http://dx.doi.org/10.1016/S0196-9781(01)00537-X" target="_blank" title="It opens in new window">CrossRef
6. Renukuntla J / et al. Approaches for enhancing oral bioavailability of peptides and proteins. Int J Pharm. 2013;447(1-):75-3. lass="external" href="http://dx.doi.org/10.1016/j.ijpharm.2013.02.030" target="_blank" title="It opens in new window">CrossRef
7. Sato AK / et al. Therapeutic peptides: technological advances driving peptides into development. Curr Opin Biotechnol. 2006;17(6):638-2. lass="external" href="http://dx.doi.org/10.1016/j.copbio.2006.10.002" target="_blank" title="It opens in new window">CrossRef
8. Latham PW. Therapeutic peptides revisited. Nat Biotechnol. 1999;17(8):755-. lass="external" href="http://dx.doi.org/10.1038/11686" target="_blank" title="It opens in new window">CrossRef
9. Luckett S / et al. High-resolution structure of a potent, cyclic proteinase inhibitor from sunflower seeds. J Mol Biol. 1999;290(2):525-3. lass="external" href="http://dx.doi.org/10.1006/jmbi.1999.2891" target="_blank" title="It opens in new window">CrossRef
10. Kalman K / et al. ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide. J Biol Chem. 1998;273(49):32697-07. lass="external" href="http://dx.doi.org/10.1074/jbc.273.49.32697" target="_blank" title="It opens in new window">CrossRef
11. Rauer H / et al. Structural conservation of the pores of calcium-activated and voltage-gated potassium channels determined by a sea anemone toxin. J Biol Chem. 1999;274(31):21885-2. lass="external" href="http://dx.doi.org/10.1074/jbc.274.31.21885" target="_blank" title="It opens in new window">CrossRef
12. Pennington MW / et al. Role of disulfide bonds in the structure and potassium channel blocking activity of ShK toxin. Biochemistry. 1999;38(44):14549-8. lass="external" href="http://dx.doi.org/10.1021/bi991282m" target="_blank" title="It opens in new window">CrossRef
13. Pennington MW / et al. Engineering a stable and selective peptide blocker of the Kv1.3 channel in T lymphocytes. Mol Pharmacol. 2009;75(4):762-3. lass="external" href="http://dx.doi.org/10.1124/mol.108.052704" target="_blank" title="It opens in new window">CrossRef
14. Grace CR / et al. Common and divergent structural features of a series of corticotropin releasing factor-related peptides. J Am Chem Soc. 2007;129(51):16102-4. lass="external" href="http://dx.doi.org/10.1021/ja0760933" target="_blank" title="It opens in new window">CrossRef
15. Fasano A. Innovative strategies for the oral delivery of drugs and peptides. Trends Biotechnol. 1998;16(4):152-. lass="external" href="http://dx.doi.org/10.1016/S0167-7799(97)01170-0" target="_blank" title="It opens in new window">CrossRef
16. Patel MM / et al. Getting into the brain: approaches to enhance brain drug delivery. CNS Drugs. 2009;23(1):35-8. lass="external" href="http://dx.doi.org/10.2165/0023210-200923010-00003" target="_blank" title="It opens in new window">CrossRef
17. Lalatsa A, Schatzlein AG, Uchegbu IF. Strategies to deliver peptide drugs to the brain. Mol Pharm. 2014;11(4):1081-3. lass="external" href="http://dx.doi.org/10.1021/mp400680d" target="_blank" title="It opens in new window">CrossRef
18. Geiger T, Clarke S. Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides. Succinimide-linked reactions that contribute to protein degradation. J Biol Chem. 1987;262(2):785-4.
19. Aswad DW. Deamidation and isoaspartate formation in peptides and proteins. In: Aswad DW, editor. - 刊物主题：Pharmacology/Toxicology; Biochemistry, general; Biotechnology; Pharmacy;
- 出版者：Springer US
- ISSN：1550-7416
文摘
Downstream success in Pharmaceutical Development requires thoughtful molecule design early in the lifetime of any potential therapeutic. Most therapeutic monoclonal antibodies are quite similar with respect to their developability properties. However, the properties of therapeutic peptides tend to be as diverse as the molecules themselves. Analysis of the primary sequence reveals sites of potential adverse posttranslational modifications including asparagine deamidation, aspartic acid isomerization, methionine, tryptophan, and cysteine oxidation and, potentially, chemical and proteolytic degradation liabilities that can impact the developability and manufacturability of a potential therapeutic peptide. Assessing these liabilities, both biophysically and functionally, early in a molecule’s lifetime can drive a more effective path forward in the drug discovery process. In addition to these potential liabilities, more complex peptides that contain multiple disulfide bonds can pose particular challenges with respect to production and manufacturability. Approaches to reducing the disulfide bond complexity of these peptides are often explored with mixed success. Proteolytic degradation is a major contributor to decreased half-life and efficacy. Addressing this aspect of peptide stability early in the discovery process increases downstream success. We will address aspects of peptide sequence analysis, molecule complexity, developability analysis, and manufacturing routes that drive the decision making processes during peptide therapeutic development.