A high-throughput screening approach to anthrax lethal factor inhibition

被引：25

作者：

Johnson, Sherida L. ^{[1
]}

Chen, Li-Hsing ^{[1
]}

Pellecchia, Maurizio ^{[1
]}

机构：

[1] Burnham Inst Med Res, La Jolla, CA 92037 USA

来源：

BIOORGANIC CHEMISTRY | 2007年 / 35卷 / 04期

关键词：

anthrax; lethal factor; high-throughput screening; Botulinum Neurotoxin;

D O I：

10.1016/j.bioorg.2006.12.005

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：

A high-throughput screening approach was used to identify new inhibitors of the metallo-protease lethal factor from Bacillus anthracis. A library of similar to 14,000 compounds was screened using a fluorescence-based in vitro assay and hits were further characterized enzymatically via measurements of IC50 and K-i values against a small panel of metallo-proteases. This study led to the identification of new scaffolds that inhibit LF and the Botulinum Neurotoxin Type A in the low micromolar range, while sparing the human metallo-proteases MMP-2 and MMP-9. Therefore, these scaffolds could be further exploited for the development of potent and selective anti-toxin agents. (c) 2007 Elsevier Inc. All rights reserved.

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页码：306 / 312

页数：7

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