| In order to enable the development of improved tandem mass spectrometry based methods for selective proteome analysis, the mechanisms, product ion structures and other factors influencing the gas-phase fragmentation reactions of methionine side chain derivatized 'fixed-charge' phenacyl sulfonium ion containing peptide ions have been examined. Dissociation of these peptide ions results in exclusive loss of the derivatized side chain, thereby enabling their selective identification. The resultant product ion(s) are then subjected to further dissociation to obtain sequence information for subsequent protein identification. Molecular orbital calculations (at the B3LYP/6-31+G** level of theory) performed on a simple peptide model, together with experimental evidence obtained by multistage dissociation of a regioselectively deuterated methionine derivatized sulfonium ion containing tryptic peptide, indicate that the initial fragmentation occurs via SN2 reactions resulting in the formation of cyclic five- and six-membered hydrofuran and oxazine product ions. Further, molecular orbital calculations and experimental evidence obtained from various para-substituted phenacyl sulfonium ion peptide ions have determined that the ratio of neutral versus charged losses of the derivatized side chain exhibits a linear dependence on the proton affinity of the side chain fragmentation product, as well as the proton mobility of the peptide product ions. |
