微生物代谢国家重点实验室-启智讲坛第二十一讲

 

报告题目：Design and discovery of enzyme inhibitors as potential therapies for diabetes

主 讲  人：Stephen G. Withers

加拿大不列颠哥伦比亚大学Khorana讲席教授

上海交通大学顾问教授、英国皇家学会院士、加拿大皇家学会院士

报告时间：4月14日（星期四） 上午9:30

报告地点：闵行校区生物药学楼树华多功能厅（800号）

联 系  人：杨广宇 This e-mail address is being protected from spambots. You need JavaScript enabled to view it.

摘要：

Carbohydrates play important roles in biological systems, not only in the form of energy storage materials such as starch, but also as “recognition elements” on cell surfaces. The degradation of such sugar structures is achieved using enzymes known as glycoside hydrolases (glycosidases). Specific enzyme inhibitors are not only useful tools for understanding enzyme mechanisms, but also can play important roles as therapeutics if inhibition suppresses unwanted reactions. I shall illustrate this with two recent examples of potent inhibitors of human amylase that we have identified as potential therapeutics for controlling blood glucose levels.

High-throughput screening of natural product extract libraries from terrestrial and marine sources, in conjunction with my colleague Ray Andersen, has yielded two new classes of potent Montbretin A (Ki = 8 nM) and Helianthamide (Ki = 10 pM) inhibitors of the human starch-digesting enzyme α-amylase. Importantly, good control of blood glucose levels is seen in diabetic rats given Montbretin A in their drinking water. Structural studies with these inhibitors reveal a new paradigm for glycosidase inhibition that we are currently exploiting and exploring.