Cascade Dissociations of Peptide Cation-Radicals. Part 1. Scope and Effects of Amino Acid Residues in Penta-, Nona-, and Decapeptides

Amino acid residue-specific backbone and side-chain dissociations of peptide z ions in MS3 spectra were elucidated for over 40 pentapeptides with arginine C-terminated sequences of the AAXAR and AAHXR type, nonapeptides of the AAHAAXX '' AR and AAHAXAX '' AR type, and AAHAAXX '' AAR decapeptides. Peptide z(n) ions containing amino acid residues with readily transferrable benzylic or tertiary beta-hydrogen atoms (Phe, Tyr, His, Trp, Val) underwent facile backbone cleavages to form dominant z(n-2) or z(n-3) ions. These backbone cleavages are thought to be triggered by a side-chain beta-hydrogen atom transfer to the z ion C-alpha radical site followed by homolytic dissociation of the adjacent C-alpha-CO bond, forming x(n-2) cation-radicals that spontaneously dissociate by loss of HNCO. Amino acid residues that do not have readily transferrable beta-hydrogen atoms (Gly, Ala) do not undergo the z(n) -> z(n-2) dissociations. The backbone cleavages compete with side-chain dissociations in z ions containing Asp and Asn residues. Side-chain dissociations are thought to be triggered by alpha-hydrogen atom transfers that activate the C-beta-C-gamma or C-beta-heteroatom bonds for dissociations that dominate the MS3 spectra of z ions from peptides containing Leu, Cys, Lys, Met, Ser, Arg, Glu, and Gln residues. The Lys, Arg, Gln, and Glu residues also participate in gamma-hydrogen atom transfers that trigger other side-chain dissociations.