Novel C(β)–C(γ) Bond Cleavages of Tryptophan-Containing Peptide Radical Cations

In this study, we observed unprecedented cleavages of the C(β)–C(γ) bonds of tryptophan residue side chains in a series of hydrogen-deficient tryptophan-containing peptide radical cations (M(•+)) during low-energy collision-induced dissociation (CID). We used CID experiments and theoretical density functional theory (DFT) calculations to study the mechanism of this bond cleavage, which forms [M – 116](+) ions. The formation of an α-carbon radical intermediate at the tryptophan residue for the subsequent C(β)–C(γ) bond cleavage is analogous to that occurring at leucine residues, producing the same product ions; this hypothesis was supported by the identical product ion spectra of [LGGGH – 43](+) and [WGGGH – 116](+), obtained from the CID of [LGGGH](•+) and [WGGGH](•+), respectively. Elimination of the neutral 116-Da radical requires inevitable dehydrogenation of the indole nitrogen atom, leaving the radical centered formally on the indole nitrogen atom ([Ind](•)-2), in agreement with the CID data for [WGGGH](•+) and [W(1-CH3)GGGH](•+); replacing the tryptophan residue with a 1-methyltryptophan residue results in a change of the base peak from that arising from a neutral radical loss (116 Da) to that arising from a molecule loss (131 Da), both originating from C(β)–C(γ) bond cleavage. Hydrogen atom transfer or proton transfer to the γ-carbon atom of the tryptophan residue weakens the C(β)–C(γ) bond and, therefore, decreases the dissociation energy barrier dramatically. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13361-011-0295-5) contains supplementary material, which is available to authorized users.