SCHEDULED MAINTENANCE
L-Methionine increases the rate of reaction of 5′-guanosine monophosphate with the anticancer drug cisplatin: mixed-ligand adducts and reversible methionine binding
Abstract
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 1H and [1H, 15N] NMR spectroscopy. Novel intermediates detected and characterized include cis-[Pt(5′-GMP-N7)(L-HMet-S)(NH3)2]2+ and [Pt(L-Met-S,N)(5′-GMP-N7)(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)Cl2](en = 1,2-diaminoethane) have also been investigated.
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