Gas-phase peptide fragmentation: How understanding the fundamentals provides a springboard to developing new chemistry and novel proteomic tools

Christopher K. Barlow, Richard A.J. O'Hair

Research output: Contribution to journalReview ArticleResearchpeer-review

38 Citations (Scopus)


This tutorial provides an overview of the evolution of some of the key concepts in the gas-phase fragmentation of different classes of peptide ions under various conditions [e.g. collision-induced dissociation (CID) and electron transfer dissociation (ETD)], and then demonstrates how these concepts can be used to develop new methods. For example, an understanding of the role of the mobile proton and neighboring group interactions in the fragmentation reactions of protonated peptides has led to the design of the 'SELECT' method. For ETD, a model based on the Landau-Zener theory reveals the role of both thermodynamic and geometric effects in the electron transfer from polyatomic reagent anions to multiply protonated peptides, and this predictive model has facilitiated the design of a new strategy to form ETD reagent anions from precursors generated via ESI. Finally, two promising, emerging areas of gas-phase ion chemistry of peptides are also described: (1) the design of new gas-phase radical chemistry to probe peptide structure, and (2) selective cleavage of disulfide bonds of peptides in the gas phase via various physicochemical approaches.

Original languageEnglish
Pages (from-to)1301-1319
Number of pages19
JournalJournal of Mass Spectrometry
Issue number10
Publication statusPublished - 1 Oct 2008
Externally publishedYes


  • Anions
  • Cations
  • Collision-induced dissociation
  • Disulfide bond
  • Electron transfer dissociation
  • Electrospray
  • Metal ions
  • Peptide
  • Radical

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