L-METHIONINE INCREASES THE RATE OF REACTION OF 5'-GUANOSINE MONOPHOSPHATE WITH THE ANTICANCER DRUG CISPLATIN - MIXED-LIGAND ADDUCTS AND REVERSIBLE METHIONINE BINDING

L-Methionine (L-HMet) increased the rate of reaction of the anticancer drug cisplatin, cis-[PtCl2(NH3)(2)], with guanosine 5'-monophosphate (5'-GMP) at pH 7. The course of the reaction has been elucidated by H-1 and [H-1, N-15] NMR spectroscopy. Novel intermediates detected and characterized include cis-[Pt(5'-GMP-N-7)(L-HMet-S)(NH3)(22)](2+) and [Pt(L-Met-S,N)(5'-GMP-N-7)(NH3)](+) (charges on 5'-GMP ignored), the formation of which involves ammine release. Monodentate S-bound L-HMet can co ordinate reversibly. whereas S,N-chelated L-Met is much less reactive. Thus. methionine residues in peptides and proteins could play a role in the transfer of Pt onto DNA. Comparative reactions of [Pt(en)Cl-2] (en = 1,2-diaminoethane) have also been