Development of robust industrial protocols for the synthesis of peptide derivatives

基于多肽的疗法在我们目前对抗疾病的武器库中占据了相当大的一部分。然而，未经修饰的多肽由于其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而不适合作为药物。为了克服这些缺点，人们已经提出了大量的努力来对未受保护的多肽进行化学修饰。这些修饰增加了有价值的特征，如增强细胞通透性，提高对蛋白酶的稳定性，提高口服生物利用度，延长在血清中的寿命，提高特异性和构象刚性以增强效力。目前，对不受保护的多肽方案的稳健快速修改仅限于学术实验室使用。工业规模的多肽衍生物合成并不常见。随着对多肽疗法的需求日益增长，TC Science Inc.的目标是开发一种适用于工业级生产的多肽修饰协议。阿尔伯塔大学的德尔达实验室在使用现成的改性剂对水中未受保护的多肽进行稳健快速修饰方面拥有丰富的经验。通过结合DERDA小组的学术优势和TC Science Inc.的行业经验，这项建议的目标是开发强大的工业多肽修饰协议。

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.