Metal-mediated inhibition is a viable approach for inhibiting cellular methionine aminopeptidase

被引：10

作者：

Chai, Sergio C. ^{[1
]}

Ye, Qi-Zhuang ^{[1
]}

机构：

[1] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 24期

基金：

美国国家卫生研究院;

关键词：

Metallohydrolase; Drug discovery; Enzyme inhibitors; X-ray structure analysis; Antibiotics; ESCHERICHIA-COLI; DISCOVERY; BINDING; GENE;

D O I：

10.1016/j.bmcl.2009.10.082

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Methionine aminopeptidase (MetAP) plays an essential role for cell survival. Hence, MetAP is a promising target for developing broad spectrum antibacterial agents. MetAP can be activated in vitro by a number of divalent metals, and X-ray structures show that the active site can accommodate two cations. Herein, we demonstrate bacterial growth inhibition by a compound that targets MetAP by recruitment of a third auxiliary metal. Contrary to previous beliefs, this shows that metal-mediated inhibition is a viable approach for discovering MetAP inhibitors that are effective for therapeutic application. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：6862 / 6864

页数：3

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