Rational design of transition-state analogues as potent enzyme inhibitors with therapeutic applications

被引：10

作者：

Amyes, Rina L. ^{[1
]}

Richard, John P. ^{[1
]}

机构：

[1] SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA

来源：

ACS CHEMICAL BIOLOGY | 2007年 / 2卷 / 11期

关键词：

D O I：

10.1021/6700228t

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The structures of the transition states for a variety of enzyme-catalyzed ribosyl group transfer reactions, determined by computational evaluation of multiple tritium and heavy atom kinetic isotope effects on these enzymatic reactions, have been found to show a considerable variation in the extent of bond cleavage at the ribosyl anomeric carbon. The calculated transition-state structures have been used to guide the design of high-affinity transition-state analogue inhibitors for 5'-methylthioadenosine nucleosidases with potential as therapeutic agents.

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页码：711 / 714

页数：4

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