Anticancer Gold(III) Porphyrins Target Mitochondrial Chaperone Hsp60. Issue 4 (9th December 2015)

• Record Type: Journal Article
• Authors: Hu, Di; Liu, Yungen; Lai, Yau‐Tsz; Tong, Ka‐Chung; Fung, Yi‐Man; Lok, Chun‐Nam; Che, Chi‐Ming
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 4(2016)
• Page Start: 1387
• Page End: 1391
• Publication Date: 2015-12-09
• Subjects: antitumor agents -- biological targets -- chemical proteomics -- gold porphyrins -- Hsp60; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201509612
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Identification of the molecular target(s) of anticancer metal complexes is a formidable challenge since most of them are unstable toward ligand exchange reaction(s) or biological reduction under physiological conditions. Gold(III) meso ‐tetraphenylporphyrin (gold‐1 a ) is notable for its high stability in biological milieux and potent in vitro and in vivo anticancer activities. Herein, extensive chemical biology approaches employing photo‐affinity labeling, click chemistry, chemical proteomics, cellular thermal shift, saturation‐transfer difference NMR, protein fluorescence quenching, and protein chaperone assays were used to provide compelling evidence that heat‐shock protein 60 (Hsp60), a mitochondrial chaperone and potential anticancer target, is a direct target ofgold‐1 a in vitro and in cells. Structure–activity studies with a panel of non‐porphyrin gold(III) complexes and other metalloporphyrins revealed that Hsp60 inhibition is specifically dependent on both the gold(III) ion and the porphyrin ligand. Abstract : Golden gun : Hsp60 is a direct molecular target of the anticancer compound gold(III) meso ‐tetraphenylporphyrin (gold‐1 a ) under both in vitro and cellular conditions, as revealed by chemical biology studies employing photo‐affinity labeling, click chemistry, proteomic identification, cellular thermal shift, saturation‐transfer difference NMR, protein fluorescence quenching, and protein chaperone assays.