NMR-STUDY OF THE INTERACTION OF PLATINUM SALTS WITH A TETRAPEPTIDE CONTAINING CYSTEINYL RESIDUES

H-1-,C-13- and Pt-195-NMR spectroscopies are used to identify the comp lexes formed between the platinum salts cis-(NH3)(2)PtCl2 (cis-DDP), t rans-(NH3)(2)PtCl2 (trans-DDP), cis-(en)Pt(ONO2)(2), and [(dien)PtBr]B r and the tetrapeptide Boc-Cys(1)(SMe)-Ser(2)-Ala(3)-Cys(4)(SMe)-CONH2 (CSAC) containing the sequence Cys-X-Y-Cys (X, Y = amino acids) and b eing a model of metallothionein (MT) and/or a model for platinum bindi ng to methionine type sulfur, known to occur in biological systems. MT , rich in cysteine is known to bind both in vivo and in vitro with the antitumor drug cis-DDP. The H-1- and C-13-NMR assignments were made b y two-dimensional homo-and heteronuclear experiments for the ligand CS AC. The S-CH3 groups coordinate through sulfur to Pt(II) in all cases. The results show that cis-DDP forms a mixture of different diastereoi somers around the sulfur chiral centers and/or polymeric species with NH3 liberation, due to the strong trans-effect of sulfur. cis-Pt(en)(O NO2)(2) forms a monomeric (1:1) chelate structure with CSAC, without e n liberation, coordinated through both sulfur atoms. However, slow en liberation could take also place upon increasing temperature. Three si gnals are observed in the H-1- and Pt-195-NMR spectra of this complex in accordance with the proposed monomeric structure. trans-DDP, on the other hand, forms a 2:1 complex with CSAC identical to the one formed by [Pt(dien)Br]Br, both coordinated to the -S-CH3 groups. No amine re lease was observed in the case of these two complexes.