Effect of the N-terminal basic residue on facile C α-C bond cleavages of aromatic-containing peptide radical cations

Abstract

Fragmentation of radical cationic peptides [R(G) n-2X(G) 7-n] + and [R(G) m-2XG] + (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-2X(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 via β-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. © the Owner Societies. 2011.