title: Structure and further fragmentation of significant [a3 + Na - H]+ ions from sodium-cationized peptides.
abstract: A good understanding of gas-phase fragmentation chemistry of peptides is important for accurate protein identification. Additional product ions obtained by sodiated peptides can provide useful sequence information supplementary to protonated peptides and improve protein identification. In this work, we first demonstrate that the sodiated a3 ions are abundant in the tandem mass spectra of sodium-cationized peptides although observations of a3 ions have rarely been reported in protonated peptides. Quantum chemical calculations combined with tandem mass spectrometry are used to investigate this phenomenon by using a model tetrapeptide GGAG. Our results reveal that the most stable [a3 + Na - H](+) ion is present as a bidentate linear structure in which the sodium cation coordinates to the two backbone carbonyl oxygen atoms. Due to structural inflexibility, further fragmentation of the [a3 + Na - H](+) ion needs to overcome several relatively high energetic barriers to form [b2 + Na - H](+) ion with a diketopiperazine structure. As a result, low abundance of [b2 + Na - H](+) ion is detected at relatively high collision energy. In addition, our computational data also indicate that the common oxazolone pathway to generate [b2 + Na - H](+) from the [a3 + Na - H](+) ion is unlikely. The present work provides a mechanistic insight into how a sodium ion affects the fragmentation behaviors of peptides.
authors.affiliation: College of Chemistry, Jilin University, Changchun, 130012, China.
authors.forename: Huixin
authors.initials: H
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Wei
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Xinhua
authors.initials: X
authors.lastname: Guo
mesh_terms: D002412:Cations / Q000737:chemistry; D005591:Chemical Fractionation; D054659:Diketopiperazines / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D010455:Peptides / Q000032:analysis* / Q000737:chemistry*; D011789:Quantum Theory; D012964:Sodium / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002412:Cations; D054659:Diketopiperazines; D007477:Ions; D010455:Peptides; D012964:Sodium
keywords: a3 ions; b2 ion structure; charge-remote fragmentation pathway; diketopiperazine; sodium-ion-associated peptide