Novel peptide ion chemistry associated with gold (I) cationization: Preferential cleavage at lysine residues

Abstract

Novel peptide ion chemistry associated with gold (I) cationization is described. Cation switching ion/ion reactions, involving gold dichloride reagent anion, [AuCl2]−, are used to replace protons with a gold (I) cation on a polypeptide. Collision induced dissociation of aurated, lysine-containing peptides results in the elimination of gold hydride and ammonia, generating a [M−H−NH3]+ oxidized species. The oxidized product is likely a cyclic iminium ion. This fragmentation pathway is specific to lysine side-chains as polypeptides containing arginine or histidine in the absence of lysine were not observed to form the oxidized product. While oxidation can occur on N-terminal, internal, and C-terminal lysine residues, it is observed to a lesser extent at lysines found at internal and C-terminal positions. However, isolation and subsequent activation of the [M−H−NH3]+ species derived from the internal or C-terminal positions results in preferential cleavage N-terminal to the oxidized lysine residue. This chemistry has been demonstrated using a variety of model peptides and has also been applied to the analysis of melittin.