Tuning the Au(I)-mediated inhibition of cathepsin B through ligand substitutions

被引：24

作者：

Gunatilleke, Shamila S. ^{[1
]}

Barrios, Amy M. ^{[1
]}

机构：

[1] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA

来源：

JOURNAL OF INORGANIC BIOCHEMISTRY | 2008年 / 102卷 / 03期

关键词：

Gold(I) complexes; rheumatoid arthritis; Cathepsins; enzyme inhibition;

D O I：

10.1016/j.jinorgbio.2007.10.019

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：

It has been over 80 years since the antiarthritic properties of gold(l) complexes were first recognized. However, a detailed understanding of their mechanism of action has been slow to develop. One likely biological target of gold(l) is the cathepsin family of lysosomal cysteine proteases, enzymes involved in the inflammation and joint destruction that are hallmarks of rheumatoid arthritis (RA). We have previously shown that analogs of auranofin, a clinically available antiarthritic drug, inhibit cathepsin B. In this study, the extent to which the steric and electronic properties of the phosphine ligand can be modified to obtain enhanced potency against cathepsin B is investigated. (C) 2007 Elsevier Inc. All rights reserved.

引用

页码：555 / 563

页数：9

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