Arginine‐Facilitated α‐ and π‐Radical Migrations in Glycylarginyltryptophan Radical Cations

Abstract

We have used model tripeptides GXW (with X being one of the amino acid residues glycine (G), alanine (A), leucine (L), phenylalanine (F), glutamic acid (E), histidine (H), lysine (K), or arginine (R)) to study the effects of the basicity of the amino acid residue on the radical migrations and dissociations of odd-electron molecular peptide radical cations M(·+) in the gas phase. Low-energy collision-induced dissociation (CID) experiments revealed that the interconvertibility of the isomers [G(·)XW](+) (radical centered on the N-terminal α-carbon atom) and [GXW](·+) (radical centered on the π system of the indolyl ring) generally increased upon increasing the proton affinity of residue X. When X was arginine, the most basic amino acid, the two isomers were fully interconvertible and produced almost identical CID spectra despite the different locations of their initial radical sites. The presence of the very basic arginine residue allowed radical migrations to proceed readily among the [G(·)RW](+) and [GRW](·+) isomers prior to their dissociations. Density functional theory calculations revealed that the energy barriers for isomerizations among the α-carbon-centered radical [G(·)RW](+), the π-centered radical [GRW](·+), and the β-carbon-centered radical [GRW(β)(·)](+) (ca. 32-36 kcal mol(-1)) were comparable with those for their dissociations (ca. 32-34 kcal mol(-1)). The arginine residue in these GRW radical cations tightly sequesters the proton, thereby resulting in minimal changes in the chemical environment during the radical migrations, in contrast to the situation for the analogous GGW system, in which the proton is inefficiently stabilized during the course of radical migration.

Gas-Phase Peptide Sulfinyl Radical Ions: Formation and Unimolecular Dissociation

“…This trend was consistently observed for over 20 singly protonated peptide sulfinyl radical ions. Similar phenomenon was observed for CID of arginine containing tripeptide radical cations [66][67][68]. Theoretical calculations by Zhao et al showed that the energy barriers for radical migration were lowered by 5-10 kcal/mol due to localization of charge on arginine sidechain, while the charge-directed dissociation barriers were increased significantly [67].…”

The Radical Ion Chemistry of S-Nitrosylated Peptides

“…: the CID mass spectrum of the Arg-containing peptide is dominated by side chain losses and c/z fragments, whereas that of the Lys-containing peptide is dominated by the y 10 fragment. Theoretical calculations of GRW radical cations by Chu and co-workers revealed that the presence of arginine facilitated radical migration [48]. The CID spectra of [G…”

Electron Capture Dissociation of Hydrogen-Deficient Peptide Radical Cations

“…Fragmentation pathways of hydrogen-deficient species in ECD were distinct from those observed in CID, IRMPD, and EID of the same species [21]. In general, in CID, IRMPD, and EID of highly charged hydrogen-deficient species fragmentation is governed by a competition between radical and chargedriven processes [10][11][12][13][14][15]21]. Abundant amino acid sidechain losses, enhanced cleavages at aromatic residues, and formation of a-, b-, c-, y-, c-, and z-type ions are observed [5,16,[20][21][22].…”

“…Dissociation of hydrogen-deficient species is determined by the competition between radical and charge driven processes [10][11][12][13][14][15]. For singly charged arginine containing radical cations, M +• , dissociation is governed by radical driven processes resulting mainly in C a -C bond cleavages and side chain losses [12,13,16].…”