Proteins as Possible Targets for Cytotoxic trans-Platinum(II) Complexes with Aliphatic Amine Ligands: Further Exceptions to the DNA Paradigm

The reactivity of three cytotoxic trans-PtII complexes bearing aliph. 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 addnl. information on the preferential Pt binding sites. To det. whether trans-PtII complexes can migrate from a peptide to an oligonucleotide, transfer expts. were also performed using ESI-MS, and competitive binding of the trans-PtII 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 obsd. In general, adduct formation with the selected peptide is favored for the trans compds., whereas cisplatin shows a preference for oligonucleotides, esp. if adjacent G-G residues are present. The results are discussed in relation to the possible mechanism of action of the trans-PtII complexes.