A metabolically stable tight-binding transition-state inhibitor of glyoxalase-I

被引：24
作者：
More, Swati S.
Vince, Robert
机构：
[1] Univ Minnesota, Coll Pharm, Ctr Drug Design, Acad Hlth Ctr, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Coll Pharm, Dept Med Chem, Minneapolis, MN 55455 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 23期
关键词：
methylglyoxal; glyoxalase; gamma-glutamyltranspeptidase; glutathione; hydroxamic acid; transition-state inhibitor;
D O I：
10.1016/j.bmcl.2006.08.121
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The design, synthesis, and enzyme kinetics evaluation of a transition-state inhibitor of glyoxalase-I is described. The union of the hydroxamic acid zinc-chelator with a urea isostere for the glu-cys amide bond led to a glutathione analog which retained inhibitory potency toward glyoxalase-I while possessing resistance toward gamma-glutamyltranspeptidase mediated breakdown. This compound is viewed as a potential lead for the development of second-generation glyoxalase-I inhibitors wherein, the problems pertaining to metabolism and selectivity are overcome. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码：6039 / 6042
页数：4
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