Arginine-facilitated isomerization : Radical-induced dissociation of aliphatic radical cationic glycylarginyl(iso)leucine tripeptides

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  • Qiang Hao
  • Tao Song
  • Dominic C. M. Ng
  • Quan Quan
  • Ivan K. Chu


Original languageEnglish
Pages (from-to)7627-7634
Journal / PublicationJournal of Physical Chemistry B
Issue number26
Publication statusPublished - 5 Jul 2012


The gas phase fragmentations of aliphatic radical cationic glycylglycyl(iso)leucine tripeptides ([G•G(L/I)]+), with well-defined initial locations of the radical centers at their N-terminal α-carbon atoms, are significantly different from those of their basic glycylarginyl(iso)leucine ([G•R(L/I)]+) counterparts; the former lead predominantly to [b2 - H]•+ fragment ions, whereas the latter result in the formation of characteristic product ions via the losses of •CH(CH3)2 from [G•RL]+ and •CH2CH3 from [G•RI]+ through Cβ-Cγ side-chain cleavages of the (iso)leucine residues, making these two peptides distinguishable. The α-carbon-centered radical at the leucine residue is the key intermediate that triggers the subsequent Cβ-Cγ bond cleavage, as supported by the absence of •CH(CH3)2 loss from the collision-induced dissociation of [G•RLα-Me]+, a radical cation for which the α-hydrogen atom of the leucine residue had been substituted by a methyl group. Density functional theory calculations at the B3LYP 6-31++G(d,p) level of theory supported the notion that the highly basic arginine residue could not only increase the energy barriers against charge-induced dissociation pathways but also decrease the energy barriers against hydrogen atom transfers in the GR(L/I) radical cations by ∼10 kcal mol-1, thereby allowing the intermediate precursors containing α- and γ-carbon-centered radicals at the (iso)leucine residues to be formed more readily prior to promoting subsequent Cβ-C γ and Cα-Cβ bond cleavages. The hydrogen atom transfer barriers for the α- and γ-carbon-centered GR(L/I) radical cations (roughly in the range 29-34 kcal mol-1) are comparable with those of the competitive side-chain cleavage processes. The transition structures for the elimination of •CH(CH3) 2 and •CH2CH3 from the (iso)leucine side chains possess similar structures, but slightly different dissociation barriers of 31.9 and 34.0 kcal mol-1, respectively; the energy barriers for the elimination of the alkenes CH2=CH(CH3)2 and CH3CH=CHCH3 through Cα-C β bond cleavages of γ-carbon-centered radicals at the (iso)leucine side chains are 29.1 and 32.8 kcal mol-1, respectively. © 2012 American Chemical Society.

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