Expanding the Toolbox for Peptide Disulfide Bond Formation via l-Methionine Selenoxide Oxidation.

Abstract

In this study, l-methionine selenoxide (MetSeO) was used as an oxidant for the construction of peptide disulfide bonds. Excellent yields for various disulfide-containing peptides were achieved via the MetSeO oxidation method in different solvents and on a resin. Most importantly, the construction of disulfide bonds can be performed in the trifluoroacetic acid cocktail used for the cleavage of peptides from the resin, which obviates the steps of peptide purification and lyophilization. This facilitates and simplifies the synthesis of disulfide-containing peptides. Kinetic and mechanistic studies of the reaction between MetSeO and dithiothreitol (DTT, a model compound of dicysteine-containing peptide) show that the reaction is first order in both [MetSeO] and [DTT], and a reaction mechanism is proposed that can help us gain insights into the reaction of the oxidative synthesis of disulfide bonds via MetSeO oxidation.