Intramolecular oxygen-18 isotopic exchange in the gas phase observed during the tandem mass spectrometric analysis of peptides

Fast atom bombardment/tandem mass spectrometry of protonated and metal cationized peptides has revealed evidence for novel intramolecular rearrangements in the gas phase. Second generation product ion scanning (MS/MS/MS) analyses of the protonated ({sup 18}O{sub 2}) analogues established that both isotope labels are located at the new C-terminus formed via the rearrangement. The kinetic energies released during the formation of the ({sup 18}O{sub 1})-and ({sup 18}O{sub 2})-labeled rearrangement products are indistinguishable, consistent with the involvement of a common intermediate. First generation product ion spectra (MS/MS) of protonated ({sup 18}O{sub 2})-peptides include fragments arising from simple peptide bond cleavage which show isotope enrichments consistent with immediate precursor ions which incorporate ({sup 18}O) at the peptide bond between the penultimate and C-terminal amino acid residues. Several lines of evidence eliminate the possibility of such incorporation of label during solution-phase preparation of the ({sup 18}O{sub 2})-labeled analogues. Thus, the combined data are in accord with an isotope exchange process occurring in the gas phase, most likely through a mechanism involving the reversible formation of a cyclic intermediate. These studies, combined with previous data, emphasize the importance of the conformations adopted by gas-phase peptide ions in influencing fragmentation pathways. 30 refs., 8 figs.