Proteins as possible targets for cytotoxic trans-platinum(II) complexes with aliphatic amine ligands: Further exceptions to the DNA paradigm.

Abstract

The reactivity of three cytotoxic trans-Pt(II) complexes bearing aliphatic amine ligands, with transferrin and single-stranded oligonucleotides as DNA models, was investigated by ESI-MS and the results obtained are discussed in comparison with cisplatin. Tandem MS studies provided additional information on the preferential Pt binding sites. To determine whether trans-Pt(II) complexes can migrate from a peptide to an oligonucleotide, transfer experiments were also performed using ESI-MS, and competitive binding of the trans-Pt(II) complexes toward a model peptide and different oligonucleotides was also investigated. Significant differences in the reactivity of the trans complexes with respect to cisplatin were observed. In general, adduct formation with the selected peptide is favored for the trans compounds, whereas cisplatin shows a preference for oligonucleotides, especially if adjacent G-G residues are present. The results are discussed in relation to the possible mechanism of action of the trans-Pt(II) complexes.