title: Proton Mobility in b₂ Ion Formation and Fragmentation Reactions of Histidine-Containing Peptides.
abstract: A detailed energy-resolved study of the fragmentation reactions of protonated histidine-containing peptides and their b2 ions has been undertaken. Density functional theory calculations were utilized to predict how the fragmentation reactions occur so that we might discern why the mass spectra demonstrated particular energy dependencies. We compare our results to the current literature and to synthetic b2 ion standards. We show that the position of the His residue does affect the identity of the subsequent b2 ion (diketopiperazine versus oxazolone versus lactam) and that energy-resolved CID can distinguish these isomeric products based on their fragmentation energetics. The histidine side chain facilitates every major transformation except trans-cis isomerization of the first amide bond, a necessary prerequisite to diketopiperazine b2 ion formation. Despite this lack of catalyzation, trans-cis isomerization is predicted to be facile. Concomitantly, the subsequent amide bond cleavage reaction is rate-limiting.
authors.affiliation: Department of Chemistry and Biochemistry, University of Missouri, St. Louis, MO, 63121, USA.
authors.forename: Carissa R
authors.initials: CR
authors.lastname: Nelson
authors.affiliation: Department of Chemistry and Biochemistry, University of Missouri, St. Louis, MO, 63121, USA.
authors.forename: Maha T
authors.initials: MT
authors.lastname: Abutokaikah
authors.affiliation: Department of Chemistry, University of Toronto, Toronto, ON, M5S 1A1, Canada.
authors.forename: Alex G
authors.initials: AG
authors.lastname: Harrison
authors.affiliation: Department of Chemistry and Biochemistry, University of Missouri, St. Louis, MO, 63121, USA. bythellb@umsl.edu.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Bythell
mesh_terms: D054659:Diketopiperazines / Q000737:chemistry*; D004151:Dipeptides / Q000737:chemistry; D006639:Histidine / Q000031:analogs & derivatives*; D007536:Isomerism; D007769:Lactams / Q000737:chemistry*; D008958:Models, Molecular; D010081:Oxazolone / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011522:Protons; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D054659:Diketopiperazines; D004151:Dipeptides; D007769:Lactams; D010455:Peptides; D011522:Protons; D010081:Oxazolone; D006639:Histidine
keywords: Diketopiperazine structure; Energy-resolved studies; Lactam structure; Oxazolone structure; b2 and a2 Ion fragmentation