Reaction of [Pt(Gly-Gly-N,N′,O)I]− with the N-acetylated dipeptide l-methionyl-l-histidine: Selective platination of the histidine side chain by intramolecular migration of the platinum(II) complex

The reaction of the monofunctional [Pt(Gly-Gly-N,N′,O)I]− complex, in which Gly-Gly is the dipeptide glycyl-glycine coordinated through two nitrogen and oxygen atoms, with the N-acetylated dipeptide l-methionyl-l-histidine (MeCOMet-His) studied by 1H NMR spectroscopy. All reactions were carried out in 50 mM phosphate buffer at pD 7.4 and at 25 °C. In the initial stage of the reaction, the platinum(II) complex forms the kinetically favored [Pt(Gly-Gly-N,N′,O)(MeCOMet-His-S)]− complex, with unidentate coordination of the MeCOMet-His dipeptide through the sulfur atom of the methionine residue. In the second stage of the reaction, complete intramolecular migration of the [Pt(Gly-Gly-N,N′,O)] unit from the sulfur to the N3 nitrogen atom of imidazole was observed and a new platinum(II)-peptide complex, [Pt(Gly-Gly-N,N′,O)(MeCOMet-His-N3)]− was formed. In comparison with previous results obtained for the reaction of [Pt(dien)Cl]+ with different methionine- and histidine-containing peptides, this migration reaction was sufficiently fast and strongly selective to the N3 atom of the imidazole ring of the histidine side chain. This study is an important step in the development of new platinum(II) complexes for selective covalent modification of peptides and proteins.

Graphical abstractIn the reaction between monofunctional [Pt(Gly-Gly-N,N′,O)I]− complex and MeCOMet-His dipeptide complete intramolecular migration of the [Pt(Gly-Gly-N,N′,O)] unit from the methionine sulfur to the N3 nitrogen atom of imidazole was observed.Figure optionsDownload full-size imageDownload as PowerPoint slide