1H N.M.R. investigations of the selective intramolecular migration of a platinum(II) complex from methionine sulfur to imidazole N 1 in N-acetylated L-methionyl-L-histidine

Abstract

Reactions of two platinum(II) complexes [Pt(dien)Cl]⁺ and [Pt(Gly-Met-S,N,N´)Cl], in which dien is diethylenetriamine and Gly-Met is the dipeptide glycyl-L-methionine coordinated through the sulfur and two nitrogen atoms, with N-acetylated dipeptide L-methionyl-L-histidine (MeCO-Met-His) have been studied by ¹H n.m.r. spectroscopy. All reactions were carried out in 50 mM phosphate buffer at pD 7.4 and at room temperature. In the initial stages of the reactions both platinum(II) complexes form a kinetically favoured platinum–peptide complex with unidentate coordination of MeCO-Met-His through the sulfur atom of the methionine residue. In the second stages of the reaction an intramolecular migration of a [Pt(dien)]²⁺ unit from the sulfur to the nitrogen atom of imidazole has been observed. This migration reaction is very slow and strongly selective to the N 1 atom of the imidazole ring of the histidine side chain. No migration of the platinum(II) complex was observed in the reaction between [Pt(Gly-Met-S,N,N´)Cl] and the dipeptide MeCO-Met-His. It was found that the latter complex, with a more sterically hindered Gly-Met ligand, reacts more slowly with thioether-containing molecules than [Pt(dien)Cl]⁺ and forms a more stable platinum–sulfur bond. This study is an important step in the development of new platinum(II) complexes for selective covalent modification of peptides and proteins.