title: Beta-scission of side-chain alkoxyl radicals on peptides and proteins results in the loss of side-chains as aldehydes and ketones.
abstract: Exposure of proteins to radicals in the presence of O(2) results in side-chain oxidation and backbone fragmentation; the interrelationship between these processes is not fully understood. Recently, initial attack on Ala side-chains was shown to give alpha-carbon radicals (and hence backbone cleavage) and formaldehyde, via the formation and subsequent beta-scission, of C-3 alkoxyl radicals. We now show that this side-chain to backbone damage transfer, is a general mechanism for aliphatic side-chains. Oxidation of Val, Leu, and Asp residues by HO(*)/O(2) results in the release of a family of carbonyls (including formaldehyde, acetone, isobutyraldehyde, and glyoxylic acid) via the formation, and subsequent beta-scission of alkoxyl radicals. The concentration of these products increases with the HO(*) flux. The release of multiple carbonyls confirms the occurrence of oxidation at C-3 and C-4 for Val, and these sites, plus C-5, for Leu. The detection of glyoxylic acid and CO(2)(-*) from Asp demonstrates the occurrence of competing beta-scission processes for the Asp C-3 alkoxyl radical. The yield of hydroperoxides and released carbonyls account for 10-145% of the initial HO(*). The greater than 100% yields confirm the occurrence of chain reactions in peptide/protein oxidation, with more than one residue being damaged per initiating radical.
authors.affiliation: The Free Radical Group, Heart Research Institute, Camperdown, Sydney, Australia.
authors.forename: Henrietta A
authors.initials: HA
authors.lastname: Headlam
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000737:chemistry; D005720:Gamma Rays / Q000009:adverse effects; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism*; D009566:Nitrates / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000528:radiation effects; D011506:Proteins / Q000737:chemistry* / Q000528:radiation effects
chemical_list: D000438:Alcohols; D000596:Amino Acids; D005609:Free Radicals; D009566:Nitrates; D010455:Peptides; D011506:Proteins; C059688:alkoxyl radical; D006861:Hydrogen Peroxide; D010100:Oxygen