Charge-remote fragmentation in a disulfide-containing peptide, [Pen]-enkephalin, under fast atom bombardment...

Fast atom bombardment collisionally activated dissociation tandem mass spectrometry (FAB CAD MS/MS) of a disulfide-containing peptide, [2-D-penicillamine, 5-D-penicillamine]- enkephalin ([Pen]-enkephalin), is described. Unlike those of most other disulfide-containing peptides investigated, CAD of the native, unreduced protonated molecule of [Pen]-enkephalin yields a relatively large number of fragment ions. Most of the peaks in the CAD spectrum represent fragmentations of the peptide backbone with 'unsymmetric' cleavage of the disulfide bond with charge retention on the N-terminus; the fragment ions generally do not contain a sulfur atom or a disulfide group. The CAD spectrum of the N-terminal ethyl-triphenylphosphonium derivative, on the other hand, shows few fragment ions and is dominated by the single peak at m/z 523. This dominant ion also results from 'unsymmetric' cleavage and corresponds to the analogous protonated species (m/z 235) in the spectrum of the underivatized peptide. The chemical method of charge localization by triphenylphosphonium derivative formation at one end of the peptide is shown to be useful for investigating fragmentation mechanisms in FAB CAD MS/MS. Comparison of the CAD spectra of derivatized and underivatized [Pen]-enkephalin suggests that charge-remote fragmentation plays a significant role in the high-energy dissociation of this disulfide-bonded peptide.