title: Dimerization of a heat shock protein 90 inhibitor enhances inhibitory activity.
abstract: 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.
authors: Department of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia. s.mcalpine@UNSW.edu.au.
authors: Hendra
authors: H
authors: Wahyudi
authors: Yao
authors: Y
authors: Wang
authors: Shelli R
authors: SR
authors: McAlpine
mesh_terms: D019281:Dimerization; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D047028:Macrocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D011092:Polyethylene Glycols / Q000737:chemistry; D058849:Protein Refolding / Q000187:drug effects; D012995:Solubility
chemical_list: D018841:HSP90 Heat-Shock Proteins; D047028:Macrocyclic Compounds; D011092:Polyethylene Glycols