title: Protein and peptide alkoxyl radicals can give rise to C-terminal decarboxylation and backbone cleavage.
abstract: Previous studies have demonstrated that gamma-irradiation of some free amino acids in the presence of oxygen gives high yields of side-chain hydroperoxides. It is shown in the present study that N-acetyl amino acids and peptides also give high levels of hydroperoxides on gamma-irradiation, even when the free amino acid does not, and that hydroperoxides can be formed on both the backbone (at alpha-carbon positions) and the side chain. Decomposition of alpha-carbon hydroperoxides by Fe(II)-EDTA gives initially an alkoxyl radical via a pseudo-Fenton reaction; these radicals fragment rapidly with k estimated as > or = 10(7) s(-1). With N-acetyl amino acids and dipeptides beta-scission of an alkoxyl radical at the C-terminal alpha-carbon results in C-terminal decarboxylation, with release of CO2.-; the corresponding amides undergo deamidation with release of .C(O)NH2. Cyclic dipeptides undergo analogous reactions with cleavage of the alpha-carbon to carbonyl-carbon bond and formation of .C(O)NHR radicals. With substrates with large aliphatic side chains, radicals from side-chain hydroperoxides are also observed. C-terminal decarboxylation and backbone fragmentation are also observed with larger peptides, amino acid homopolymers, and proteins. These observations suggest that alpha-carbon alkoxyl radicals may be key intermediates in the fragmentation of proteins in the presence of oxygen. The radicals released in these processes may react further to form O2.-, or redox cycle metal ions. These reactions may be propagating processes during protein chain oxidation.
authors.affiliation: Heart Research Institute, Sydney, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Davies
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000528:radiation effects; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D005720:Gamma Rays; D010455:Peptides / Q000737:chemistry / Q000528:radiation effects; D011506:Proteins / Q000737:chemistry* / Q000528:radiation effects
chemical_list: D000596:Amino Acids; D005609:Free Radicals; D010455:Peptides; D011506:Proteins