Interactions of antitumoral platinum-group metallodrugs with albumin

A full understanding of the modes of action of the metal-based antitumoral drugs requires the study of their interactions with all possible biological targets, including aminoacids, hormones, peptides and proteins. Albumin is the most abundant plasma protein and it is reasonable to expect that any injected metal drug will present some kind of interaction with this macromolecule, which could crucially determine its bioavailability and toxicology. However, relatively few detailed mechanistic studies have been performed on such interactions, in comparison to studies with DNA and nucleobases. In this work is presented a review of the research on reactions of platinum(II) and (IV), gold(I) and (III), ruthenium(III) and rhodium(II) antitumoral compounds with serum albumin. Generally, platinum and gold compounds are found to react with S-donors such as methionine and the Cys34 residues of albumin, the latter being the most abundant free thiol in blood plasma. Complexes of ruthenium and rhodium are thought to react mainly through coordination with imidazole groups from histidine residues. (C) 2002 Elsevier Science B.V. All rights reserved.