A new role for old ligands: Discerning chelators for zinc metalloproteinases

被引：81

作者：

Jacobsen, FE ^{[1
]}

Lewis, JA ^{[1
]}

Cohen, SM ^{[1
]}

机构：

[1] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2006年 / 128卷 / 10期

关键词：

D O I：

10.1021/ja057957s

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

In an effort to identify promising non-hydroxamate inhibitors of matrix metalloproteinases (MMPs) several new zinc-binding groups (ZBGs) based on pyridine-derived or aza-macrocycle chelators have been examined. Fluorescence-based enzyme assays have been used to determine the IC50 values for these ZBGs against MMP-1, MMP-3, and anthrax lethal factor (LF). Many of these ligands were found to be remarkably potent, with IC50 values as much as 185-fold lower than that found for acetohydroxamic acid. These ligands are proposed to be more selective warheads" for the inhibition of metalloenzymes that contain Zn2+ versus other metal ions at their active site. Copyright © 2006 American Chemical Society."

引用

页码：3156 / 3157

页数：2

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