Arginine-Facilitated Isomerization: Radical-Induced Dissociation of Aliphatic Radical Cationic Glycylarginyl(iso)leucine Tripeptides

作者：Hao, Qiang; Song, Tao; Ng, Dominic C. M.; Quan, Quan; Siu, Chi-Kit^*; Chu, Ivan K.

来源：Journal of Physical Chemistry B, 2012, 116(26): 7627-7634.

DOI：10.1021/jp301882p

• ELECTRON-CAPTURE DISSOCIATION
• GAS-PHASE FRAGMENTATION
• PEPTIDE FRAGMENTATION
• SECONDARY STRUCTURE
• PRODUCT IONS
• AMINO-ACIDS
• BASIS-SETS
• GLYCINE
• BOND
• GENERATION

The gas phase fragmentations of aliphatic radical cationic glycylglycyl(iso)leucine tripeptides ([G(center dot)G(L/I](+)), with well-defined initial locations of the radical centers at their N-terminal alpha-carbon atoms, are significantly different from those of their basic glycylarginyl(iso)leucine ([G(center dot)R(L/I)](+)) counterparts; the former lead predominantly to [b(2) - H](center dot+) fragment ions, whereas the latter result in the formation of characteristic product ions via the losses of (CH)-C-center dot(CH3)(2) from [G(center dot)RL](+) and (CH2CH3)-C-center dot from [G center dot RI](+) through C-beta-C-gamma side-chain cleavages of the (iso)leucine residues, making these two peptides distinguishable. The alpha-carbon-centered radical at the leucine residue is the key intermediate that triggers the subsequent C-beta-C-gamma bond cleavage, as supported by the absence of (CH)-C-center dot(CH3)(2) loss from the collision-induced dissociation of [G(center dot)RL(alpha-Me)](+), a radical cation for which the alpha-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 similar to 10 kcal mol(-1), thereby allowing the intermediate precursors containing alpha- and gamma-carbon-centered radicals at the (iso)leucine residues to be formed more readily prior to promoting subsequent C-beta-C-gamma and C-alpha-C-beta bond cleavages. The hydrogen atom transfer barriers for the alpha- and gamma-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)-C-center dot(CH3)(2) and (CH2CH3)-C-center dot 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 C-alpha-C-beta bond cleavages of gamma-carbon-centered radicals at the (iso)leucine side chains are 29.1 and 32.8 kcal mol(-1), respectively.

• 出版日期2012-7-5
• 单位香港城市大学; 香港中文大学