title: Reactions of model proteins with aurothiomalate, a clinically established gold(I) drug: The comparison with auranofin.
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.
authors: Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Iran; Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors: Farivash
authors: F
authors: Darabi
authors: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors: Tiziano
authors: T
authors: Marzo
authors: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors: Lara
authors: L
authors: Massai
authors: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors: Federica
authors: F
authors: Scaletti
authors: Mass Spectrometry Centre (CISM), University of Florence, Via U. Schiff 6, 50019 Sesto Fiorentino, Italy.
authors: Elena
authors: E
authors: Michelucci
authors: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: luigi.messori@unifi.it.
authors: Luigi
authors: L
authors: Messori
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001310:Auranofin / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism*; D006052:Gold Sodium Thiomalate / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D006052:Gold Sodium Thiomalate; D001310:Auranofin; D045304:Cytochromes c; D012259:Ribonuclease, Pancreatic; D009113:Muramidase
keywords: Auranofin; Aurothiomalate; Mass spectrometry; Proteins