Selective Disulfide Bond Cleavage in Gold(I) Cationized Polypeptide Ions Formed via Gas-Phase Ion/Ion Cation Switching

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Abstract
Gaseous multiply protonated disulfide-linked peptides have been subjected to reactions with AuCl2- ions to explore the possibility of effecting cation switching of Au+ for two protons and to determine whether cationization by Au+ ions affords selective dissociation of disulfide linkages. The incorporation of Au+ into several model disulfide-linked peptides proved to be straightforward. The primary ion/ion reaction channels were proton transfer, which does not lead to Au+ incorporation, and attachment of AuCl2- ions to the polypeptide cation, which does incorporate Au+. Fragmentation of the attachment product, the extent of which varied with peptide and charge state, led to losses of one or more molecules of HCl and, to some extent, cleavage of polypeptides at the disulfide linkage into its two constituent chains. Collisional activation of the intact metal-ion-incorporated peptides showed cleavage of the disulfide linkage to be a major, and in some cases exclusive, process. Cations with protons as the only cationizing agents showed only small contributions from cleavage of the disulfide linkage. These results indicate that Au+ incorporation into a disulfide-linked polypeptide ion is a promising way to effect selective dissocation of disulfide bonds. Cation switching via ion/ion reactions is a convenient means for incorporating gold and is attractive because it avoids the requirement of adding metal salts to the analyte solution. Keywords: disulfide-linked peptides • ion/ion chemistry • gold(I) cationization • tandem mass spectrometry