Reduction of platinum(IV) prodrug model complex trans-[PtCl2(CN)(4)](2-) by a peptide containing cysteine and methionine groups: HPLC and MS studies

摘要

A peptide containing cysteine and methionine groups was synthesized according to the standard Fmoc method. The reaction between a platinum(IV) prodrug model complex trans-[PtCl2(CN)(4)](2-) and the peptide was studied by high-performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS). The two cysteines in the peptide were oxidized to an intramolecular disulfide bond, while thioether of methionine was oxidized to its sulfoxide derivative. A novel intermediate was observed and characterized by HPLC and MS, and then generated methionine sulfoxide derivate through a redox reaction. The intermediate was formed through substitution of a axially chloride ligand in the Pt(IV) complex by the sulfur atom of the methionine residue. Accordingly, an oxidation mechanism was proposed for the redox reaction, which is helpful for understanding the reduction processes of similar Pt(IV) agents. (C) 2017 Elsevier B.V. All rights reserved.