微生物代謝國家重點實驗室-啟智講壇第二十一講

報告題目：Design and discovery of enzyme inhibitors as potential therapies for diabetes

主 講  人：Stephen G. Withers

加拿大不列顛哥倫比亞大學Khorana講席教授

EON体育4顧問教授🎶、英國皇家學會院士、加拿大皇家學會院士

報告時間👨🏿‍💻：4月14日（星期四） 上午9:30

報告地點⚪️：閔行校區生物藥學樓樹華多功能廳（800號）

聯 系  人：楊廣宇 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.