The reduction of oxidized methionine residues in peptidethioesters with NH4I–Me2S

Abstract

Oxidized methionine residues in peptide thioesters can be reduced rapidly with NH₄I to the corresponding sulfide by using Me₂S as coreductant. Comparative reduction studies employing a 28-amino acid peptide thioester with an N-terminal methionine oxide as model system revealed the importance of the Me₂S addition to avoid hydrolysis of the reactive thioester functionality. In addition, an NH₄I–Me₂S containing cleavage cocktail has been used for the global deprotection of various thioesters which revealed no hydrolysis or oxidative side products. These results demonstrate the general applicability of sulfoxides as protecting groups in advanced peptide synthesis techniques by facilitating the preparation and handling of methionine containing peptide thioesters for native chemical ligation (NCL).