主讲人：Stephen G. Withers

       加拿大不列颠哥伦比亚大学教授

       英国皇家学会院士

       加拿大皇家学会院士

       UBC高通量生物学中心主任

时间：2014年4月25号（星期五）09:30

地点：闵行校区生物药学楼树华多功能厅（800号）

主讲人简介：

Stephen G. Withers教授是加拿大不列颠哥伦比亚大学Khorana讲席教授、英国皇家学会院士、加拿大皇家学会院士、加拿大化学会院士，现任加拿大化学生物首席研究科学家(Canada Research Chair)，UBC高通量生物学中心主任。他主要从事糖类代谢酶的作用机制、糖类合成酶分子改造、糖代谢酶小分子药物设计研究。他在糖化学生物领域有着卓越成就和重大影响。1992年获加拿大皇家学会卢瑟福奖，2002年获国际碳水化合物组织惠斯勒奖，2012年获英国皇家学会百年奖。

报告摘要：

Glycans on the surfaces of cells play key roles in the interaction of that cell with its environment, primarily through interaction with specific protein-based receptors. Study of these interactions requires access to these complex glycans, while interference with these interactions, most likely through the use of competing glycans, is a possible therapeutic approach. Such studies require synthesis of glycans, and on a large scale in the case of therapeutics. Traditional routes to the enzymatic synthesis of oligosaccharides have either involved the use of Nature’s own biosynthetic enzymes, the glycosyl transferases, or glycosidases run in transglycosylation mode. Each approach has its drawbacks. Glycosynthases are mutant glycosidases in which the catalytic nucleophile has been removed. When used in conjunction with glycosyl fluorides of the opposite anomeric configuration to that of the substrate, these enzymes function as highly efficient transferases, frequently giving stoicheometric yields. Thioglycoligases are a new class of mutant glycosidases in which the acid/base catalyst has been mutated. These enzymes synthesise sulfur-linked oligosaccharides when an activated donor is used in conjunction with a thiosugar acceptor. Recent results in the engineering of these two classes of mutant enzymes, as well as of “classical” glycosyl transferases, will be discussed. Particular attention will be paid to their application to oligosaccharides and glycolipids. Emphasis will be placed upon the directed evolution of these enzymes using a variety of screening methodologies including robot-assisted ELISA assays and FACS cell sorting.