, Volume 16, Issue 9, pp 1523-1535

Experimental and theoretical investigations of the loss of amino acid side chains in electron capture dissociation of model peptides

Abstract

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.

Published online July 14, 2005