Development of robust industrial protocols for the synthesis of peptide derivatives

基于肽的疗法构成了我们目前对抗疾病和病症的重要部分。然而，未经修饰的肽不适合作为药物，因为它们的化学和物理稳定性差，循环血浆半衰期短，口服生物利用度有限。为了克服这些缺点，已经进行了大量的努力来化学修饰未保护的肽。这些修饰增加了有价值的特性，例如增强的细胞渗透性，增加的蛋白酶稳定性，增加的口服生物利用度，延长的血清中的寿命，改善的特异性和构象刚性以增加效力。目前，无保护肽方案的稳健快速修改仅限于学术实验室使用。肽衍生物的工业规模合成并不常见。随着肽类药物需求的增长，TC Scientific Inc.旨在开发一种适合工业化生产的肽修饰方案。阿尔伯塔大学的Derda实验室在使用现成的修饰剂对水中未受保护的肽进行快速修饰方面拥有丰富的经验。通过结合德达集团的学术优势和TC科学公司的行业经验，该提案的目标是开发稳健的工业肽修饰方案。

Peptide based therapeutics make up a significant portion of the current armory we have against diseases andillnesses. However, unmodified peptides are not suitable as drugs because of their poor chemical and physicalstability, short circulating plasma half-life, and limited oral bioavailability. To circumvent these disadvantages,a significant amount of effort has been put forward to chemically modify unprotected peptides. Thesemodifications add valuable characteristics such as enhanced cell permeability, increased stability to proteases,increased oral bioavailability, extended lifetime in the blood serum, improved specificity and conformationalrigidity to augment potency. Currently, robust rapid modification of unprotected peptide protocols are limitedto solely academic laboratory use. Industry-scale syntheses of peptide derivatives are not common. With thegrowing need in peptide-based therapeutics, TC Scientific Inc. aims to develop a peptide modification protocolthat is suitable for industry level production. The Derda Lab at the University of Alberta has extensiveexperience in robust rapid modification of unprotected peptides in water using readily available modifiers. Bycombining the academic advantage of the Derda group and the industry experience from TC scientific Inc., thegoal of this proposal is to develop robust industrial peptide modification protocols.