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

• Published in: Journal of the American Society for Mass Spectrometry Vol. 16; no. 9; pp. 1523 - 1535
• Main Authors: Fung, Y.M. Eva, Chan, T.-W. Dominic
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-09-2005; Elsevier Science; Springer Nature B.V
• Subjects: Amides; Amino Acid Sequence; Amino acids; Amino Acids - chemistry; Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; Beta decay; Binding sites; Biological and medical sciences; Carbon; Chains; Chemistry; Computer Simulation; Crystal structure; Electron capture; Electron Transport; Electrons; Exact sciences and technology; Fragments; Free Radicals - chemistry; Fundamental and applied biological sciences. Psychology; Leucine; Mass spectrometry; Models, Chemical; Models, Molecular; Molecular Sequence Data; Organic chemistry; Peptide Mapping - methods; Peptides; Peptides - chemistry; Protein Conformation; Proteins; Reactivity and mechanisms; Residues; Spectrometry, Mass, Electrospray Ionization - methods; Collisional activation; Oligopeptides; Peptides; Ab initio method; Reaction path; Theoretical study; Fragmentation pattern; Experimental study; Electron capture; α-Aminoacid; Side chain; Mass spectrometry MS/MS; Density functional method
• ISSN: 1044-0305; 1879-1123
• DOI: 10.1016/j.jasms.2005.05.001

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–C
α 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.