Dimerization of a heat shock protein 90 inhibitor enhances inhibitory activity

被引：4
|
作者：
Wahyudi, Hendra [1 ]
Wang, Yao [1 ]
McAlpine, Shelli R. [1 ]
机构：
[1] Univ New S Wales, Dept Chem, Sydney, NSW 2052, Australia
来源：
ORGANIC & BIOMOLECULAR CHEMISTRY | 2014年 / 12卷 / 05期
基金：
澳大利亚国家健康与医学研究理事会;
关键词：
SMALL-MOLECULE; SANSALVAMIDE; HSP90; CHAPERONE; DERIVATIVES; BINDING; HEAT-SHOCK-PROTEIN-90; CYTOTOXICITY; CONFORMATION; GELDANAMYCIN;
D O I：
10.1039/c3ob41722k
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
Heat shock protein 90 (hsp90) accounts for 1-2% of the total proteins in normal cells and it functions as a dimer. Hsp90 behaves as a molecular chaperone that folds, assembles, and stabilizes client proteins. We have developed a novel hsp90 inhibitor, and herein we describe the synthesis and biological activity of the dimerized variant of this inhibitor. Tethering a monomer inhibitor together produced a dimerized compound that more effectively inhibits hsp90 over the monomer.
引用
收藏
页码：765 / 773
页数：9
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