旧配体的新角色：锌金属蛋白酶的识别螯合剂

A new role for old ligands: discerning chelators for zinc metalloproteinases.

作者信息

Jacobsen Faith E, Lewis Jana A, Cohen Seth M

机构信息

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.

出版信息

J Am Chem Soc. 2006 Mar 15;128(10):3156-7. doi: 10.1021/ja057957s.

DOI:10.1021/ja057957s

PMID:16522091

Abstract

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.

摘要

为了鉴定有前景的基质金属蛋白酶（MMPs）非异羟肟酸抑制剂，人们研究了几种基于吡啶衍生或氮杂大环螯合剂的新型锌结合基团（ZBGs）。基于荧光的酶分析已用于确定这些ZBGs对MMP-1、MMP-3和炭疽致死因子（LF）的IC50值。发现许多这些配体具有显著的效力，其IC50值比乙酰氧肟酸低多达185倍。这些配体被认为是更具选择性的“弹头”，用于抑制在其活性位点含有Zn2+而非其他金属离子的金属酶。