Study of the gas-phase fragmentation behaviour of sulfonated peptides

Abstract

A series of singly and doubly protonated peptides bearing sulfonated residue have been studied, using both experiment and molecular modelling, to elucidate fragmentation chemistry of sulfonated peptides. Collision-induced dissociation mass spectra indicate that the sulfo group loss (neutral loss of 80Da) is the dominant dissociation channel. Modelling results suggest the proton transfer mechanism, where upon vibrational excitation, the acidic side chain proton is transferred from the sulfo group hydroxyl to the ester oxygen resulting in SO bond cleavage and formation of the unmodified hydroxyl containing residue and SO3. Conformations associated with potential energy profile of the reaction imply the charge remote nature of the proposed mechanism. The proposed proton transfer mechanism was compared with the intramolecular nucleophilic substitution (SN2) mechanism, the main pathway suggested for neutral loss of phosphoric acid from phosphopeptides. Both pathways (proton transfer and SN2) are available for sulfonated and phosphorylated peptides; however, each posttranslational modification favours different mechanism. The change of the bond dissociation enthalpies and the ability of stabilising the transition state structures are demonstrated as main factors responsible for each posttranslational modification activating a different pathway.