Leaving group effects on the selectivity of the gas-phase fragmentation reactions of side chain fixed-charge-containing peptide ions

Kade D. Roberts, Gavin E. Reid

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21 Citations (Scopus)

Abstract

The effect of trialkylsulfonium versus quaternaryalkylammonium ions on the multistage gas-phase fragmentation reactions of side chain, fixed-charge, cysteine-containing peptides has been examined in a quadrupole linear ion trap. These tandem mass spectrometry experiments reveal that selective loss of dialkylsulfide from fixed-charge sulfonium ion derivatives is the dominant fragmentation pathway regardless of the degree of proton mobility, indicating that it is the most energetically favored fragmentation pathway. In contrast, the loss of trimethylamine from the side chain of fixed-charge ammonium-ion-containing cysteine derivatives appears to be less energetically favored, and as a result extensive charge-remote fragmentation is observed under low proton mobility conditions, while under conditions of high proton mobility, amide bond fragmentation reactions dominate. These findings are supported by molecular orbital calculations at the B3LYP/6-31 + G(d, p) level of theory, which showed that the neutral loss of dimethylsulfide is both thermodynamically and kinetically preferred over the loss of trimethylamine.

Original languageEnglish
Pages (from-to)187-198
Number of pages12
JournalJournal of Mass Spectrometry
Volume42
Issue number2
DOIs
Publication statusPublished - 1 Feb 2007
Externally publishedYes

Keywords

  • Fragmentation mechanisms
  • Molecular orbital calculations
  • MS/MS
  • Peptide derivatization
  • Proteomics
  • Tandem mass spectrometry

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