期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 55, 期 22, 页码 10177-10186出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm301273u
关键词
-
资金
- Canadian Institutes of Health Research (CIHR) [(FRN) 111082]
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Tier 1 Canada Research Chair
- Department of Energy, Office of Biological and Environmental Research
- National Institutes of Health, National Center for Research Resources, Biomedical Technology Program
- National Institutes of Health, National Institute of General Medical Sciences
The increasing prevalence of diabetes has accelerated the search for new drugs derived from natural sources. To define the functional features of two such families of compounds, the flavonols and the ethyl caffeates, we have determined the high-resolution structures of representative inhibitors in complex with human pancreatic alpha-amylase. Myricetin binds at the active site and interacts directly with the catalytic residues despite its bulky planar nature. Notably, it reduces the normal conformational flexibility of the adjacent substrate binding cleft. In contrast, bound ethyl caffeate acts by disordering precisely those polypeptide chain segments that make up the active site binding cleft. It also operates from binding sites far removed from the active site, a property not observed in any other class of human alpha-amylase inhibitor studied to date. Given the current inadequacy of drugs directed at diabetes, the use of optimized flavonols and ethyl caffeates may present an alternative therapeutic route.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据