Reactions of model proteins with aurothiomalate, a clinically established gold(I) drug: The comparison with auranofin.

Reactions of model proteins with aurothiomalate, a clinically established gold(I) drug: The comparison with auranofin. J Inorg Biochem. 2015 Apr 1; Authors: Darabi F, Marzo T, Massai L, Scaletti F, Michelucci E, Messori L Abstract Aurothiomalate (AuTm) is an old, clinically established, antiarthritic gold drug that is currently being reconsidered as a candidate drug for cancer treatment and for other therapeutic indications within a more general drug repositioning program. As the biological effects of gold drugs seem to be mediated, mainly, by their interactions with protein targets we have analyzed here, in detail, the metalation patterns produced by aurothiomalate in a few model proteins. In particular, the reactions of aurothiomalate with the small proteins ribonuclease A, cytochrome c and lysozyme were explored through ESI MS (electrospray ionization mass spectrometry) analysis. Notably, characteristic and rather constant features emerged in the protein metalation patterns induced by AuTm that are markedly distinct from those caused by auranofin; a non-covalent interaction mode is invoked for AuTm binding to the mentioned proteins. The affinity constants of AuTm toward the three mentioned proteins were also initially assessed. The implications of the present findings are discussed. PMID: 25865000 [PubMed - as supplied by publisher]
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research