Experimental and Theoretical Investigations of the Loss of Amino Acid Side Chains in Electron Capture Dissociation of Model Peptides

Loss of side chains from different amino acid residues in a model peptide framework of RGGGXGGGR under electron capture dissociation conditions were systematically investigated, where X represents one of the twenty common amino acid residues. The α-carbon radical cations initially formed by N-Cα cleavage of peptide ions were shown to undergo secondary dissociation through losses of even-electron and/or odd-electron side-chain moieties. Among the twenty common amino acid residues studied, thirteen of them were found to lose their characteristic side chains in terms of odd-electron neutral fragments, and nine of them were found to lose even-electron neutral side chains. Several generalized dissociation pathways were proposed and were evaluated theoretically with truncated leucine-containing models using ab initio calculations at B3-PMP2/6-311 ++ G(3df,2p)//B3LYP/6-31 ++ G(d,p) level. Elimination of odd-electron side chain was associated with the initial abstraction of the hydrogen from the α-carbon bearing the side chain by the N-terminal α-carbon radical. Subsequent formation of α-β carbon-carbon double bond leads to the elimination of the odd-electron side chain. The energy barrier for this reaction pathway was 89 kJmol−1. This reaction pathway was 111 kJmol−1 more favorable than the previously proposed pathway involving the formation of cyclic lactam. Elimination of even-electron side chain was associated with the initial abstraction of the γ-hydrogen from the side chain by the N-terminal α-carbon radical. Subsequent formation of β-γ carbon-carbon double bond leads to the elimination of the even-electron side chain and the migration of the radical center to the α-carbon. The energy barrier for this fragmentation reaction was found to be 50 kJmol−1.