title: Effect of the N-terminal basic residue on facile Cα-C bond cleavages of aromatic-containing peptide radical cations.
abstract: Fragmentation of radical cationic peptides [R(G)(n-2)X(G)(7-n)]˙(+) and [R(G)(m-2)XG]˙(+) (X = Phe or Tyr; m = 2-5; n = 2-7) leads selectively to a(n)(+) product ions through in situ C(α)-C peptide backbone cleavage at the aromatic amino acid residues. In contrast, substituting the arginine residue with a less-basic lysine residue, forming [K(G)(n-2)X(G)(7-n)]˙(+) (X = Phe or Tyr; n = 2-7) analogs, generates abundant b-y product ions; no site-selective C(α)-C peptide bond cleavage was observed. Studying the prototypical radical cationic tripeptides [RFG]˙(+) and [KFG]˙(+) using low-energy collision-induced dissociation and density functional theory, we have examined the influence of the basicity of the N-terminal amino acid residue on the competition between the isomerization and dissociation channels, particularly the selective C(α)-C bond cleavage viaβ-hydrogen atom migration. The dissociation barriers for the formation of a(2)(+) ions from [RFG]˙(+) and [KFG]˙(+)via their β-radical isomers are comparable (33.1 and 35.0 kcal mol(-1), respectively); the dissociation barrier for the charge-induced formation of the [b(2)- H]˙(+) radical cation from [RFG]˙(+)via its α-radical isomer (39.8 kcal mol(-1)) was considerably higher than that from [KFG]˙(+) (27.2 kcal mol(-1)). Thus, the basic arginine residue sequesters the mobile proton to promote the charge-remote selective C(α)-C bond cleavage by energetically hindering the competing charge-induced pathways.
authors.affiliation: Department of Chemistry, The University of Hong Kong, Hong Kong, China.
authors.forename: Minijie
authors.initials: M
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Song
authors.forename: Quan
authors.initials: Q
authors.lastname: Quan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hao
authors.forename: Dei-Cai
authors.initials: DC
authors.lastname: Fang
authors.forename: Chi-Kit
authors.initials: CK
authors.lastname: Siu
authors.forename: Ivan K
authors.initials: IK
authors.lastname: Chu
mesh_terms: D002412:Cations / Q000737:chemistry; D003198:Computer Simulation; D013058:Mass Spectrometry; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D002412:Cations; D010455:Peptides