Fragmentation Patterns and Mechanisms of Singly and Doubly Protonated Peptoids Studied by Collision Induced Dissociation

Jianhua Ren, Yuan Tian, Ekram Hossain, Michael D. Connolly

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Peptoids are peptide-mimicking oligomers consisting of N-alkylated glycine units. The fragmentation patterns for six singly and doubly protonated model peptoids were studied via collision-induced dissociation tandem mass spectrometry. The experiments were carried out on a triple quadrupole mass spectrometer with an electrospray ionization source. Both singly and doubly protonated peptoids were found to fragment mainly at the backbone amide bonds to produce peptoid B-type N-terminal fragment ions and Y-type C-terminal fragment ions. However, the relative abundances of B- versus Y-ions were significantly different. The singly protonated peptoids fragmented by producing highly abundant Y-ions and lesser abundant B-ions. The Y-ion formation mechanism was studied through calculating the energetics of truncated peptoid fragment ions using density functional theory and by controlled experiments. The results indicated that Y-ions were likely formed by transferring a proton from the C-H bond of the N-terminal fragments to the secondary amine of the C-terminal fragments. This proton transfer is energetically favored, and is in accord with the observation of abundant Y-ions. The calculations also indicated that doubly protonated peptoids would fragment at an amide bond close to the N-terminus to yield a high abundance of low-mass B-ions and high-mass Y-ions. The results of this study provide further understanding of the mechanisms of peptoid fragmentation and, therefore, are a valuable guide for de novo sequencing of peptoid libraries synthesized via combinatorial chemistry.

Original languageEnglish (US)
Pages (from-to)646-661
Number of pages16
JournalJournal of the American Society for Mass Spectrometry
Volume27
Issue number4
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

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Keywords

  • CID
  • Fragmentation mechanism
  • Fragmentation pattern
  • N-alkylated glycine
  • Peptoid
  • Protonated
  • Y-ion formation mechanism

ASJC Scopus subject areas

  • Structural Biology
  • Spectroscopy

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