Inhibition of the proteolytic activity of anthrax lethal factor by aminoglycosides

被引：37

作者：

Lee, LV

Bower, KE

Liang, FS

Shi, J

Wu, D

Sucheck, SJ

Vogt, PK

Wong, CH

机构：

[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Skaggs Inst Biol Chem, Dept Mol & Expt Med, Div Oncol, La Jolla, CA 92037 USA

[3] Optimer Pharmaceut Inc, San Diego, CA 92121 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2004年 / 126卷 / 15期

关键词：

D O I：

10.1021/ja0495359

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The anthrax lethal factor (LF), a Zn-dependent endopeptidase, is considered the dominant virulence factor of anthrax. Because pharmacological inhibition of the catalytic activity of LF is considered a plausible mechanism for preventing the lethality of anthrax, a high-throughput screening experiment based on LF-catalyzed cleavage of a fluorescent substrate was performed to identify novel inhibitors of LF. The RNA-targeting antibiotics, neomycin B and some synthetic dimeric aminoglycosides, were found to be nanomolar active-site inhibitors of LF. Copyright © 2004 American Chemical Society.

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页码：4774 / 4775

页数：2

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