Formation of peptide disulfide bonds through a trans-dibromido-Pt(IV) complex oxidation reaction: Kinetic and mechanistic analyses

Abstract

A trans-dibromido-Pt(IV) complex [PtBr2(en)2]Br2 was synthesized and evaluated for the synthesis of peptide disulfide bonds in this work. The reactions between the Pt(IV) complex and dicysteine-containing peptides were carried out in various aqueous solutions. As a result, excellent yields with fast reaction rates were achieved. Methionine residue was intact when the Pt(IV) complex reacted with a dicysteine and methionine-containing peptide. 3,6-Dioxa-1,8-octanedithiol (DODT) was selected as a model compound of the dicysteine-containing peptide. Kinetic studies for the reaction between the Pt(IV) complex and DODT were performed in different pH solutions. It is first-order both in [Pt(IV)] and in [DODT]. A reaction mechanism was proposed accordingly. The kinetic and mechanistic results demonstrated that the reaction rate for the formation of peptide disulfide bond via the Pt(IV) oxidation is increased with the increase of pH of the reaction medium. The protolytic constants of the two thiol groups in peptide also play a critical role in reaction rate. On the other hand, kinetic studies demonstrated that the Pt(IV) complex trans-[PtBr2(en)2]2+ can be used in an acidic medium for the purpose of synthesis of disulfide bonds.