title: Fragmentation Patterns and Mechanisms of Singly and Doubly Protonated Peptoids Studied by Collision Induced Dissociation.
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. Graphical Abstract ᅟ.
authors.affiliation: Department of Chemistry, University of the Pacific, 3601 Pacific Avenue, Stockton, CA, 95211, USA. jren@pacific.edu.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Chemistry, University of the Pacific, 3601 Pacific Avenue, Stockton, CA, 95211, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Chemistry, University of the Pacific, 3601 Pacific Avenue, Stockton, CA, 95211, USA.
authors.forename: Ekram
authors.initials: E
authors.lastname: Hossain
authors.affiliation: The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Connolly
mesh_terms: D000478:Alkylation; D005998:Glycine / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D034444:Peptoids / Q000737:chemistry*; D011522:Protons; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D007477:Ions; D034444:Peptoids; D011522:Protons; D005998:Glycine
keywords: CID; Fragmentation mechanism; Fragmentation pattern; N-alkylated glycine; Peptoid; Protonated; Y-ion formation mechanism
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