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

• Study of the interaction of aurothiomalate with model proteins through ESI MS analysis
• Non-covalent interaction between aurothiomalate tetrameric form and model proteins
• Investigation of the effect of GSH on the protein metalation process
• Different modes of interaction of aurothiomalate and auranofin with proteins

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.

The reactions of aurothiomalate, antiarthritic gold drug, with the small proteins RNase A, cytochrome c and lysozyme were explored, principally through ESI MS analysis.Figure optionsDownload as PowerPoint slide