title: Superoxide radical anions protect enkephalin from oxidation if the amine group is blocked.
abstract: The pentapeptide methionine-enkephalin (Met-enk) is a natural opiate that inhibits signals of pain. The N-terminal tyrosyl residue is important in the recognition of the peptide by its receptor. In oxidative stress, this residue can be oxidized by reactive oxygen species. The one-electron oxidation of Met-enk and of tert-butoxycarbonyl-methionine-enkephalin (Boc-Met-enk) was studied by gamma- and pulse radiolysis in the absence and in the presence of superoxide radical anions (O(2)(.-)) and oxygen, using azidyl radicals as oxidants. Without oxygen, both peptides behaved similarly. The tyrosyl radical resulting from the oxidation of tyrosyl residue produced the dimer linked by dityrosines. Methionine was also oxidized to its sulfoxide; however, this reaction is of minor importance. When O(2)(.-) was present, it added to tyrosyl radical giving a hydroperoxide. For Met-enk, this adduct cyclized via an intramolecular Michael addition of the amine on the aromatic ring. Conversely, for Boc-Met-enk, the adduct eliminated oxygen which led to 97% regeneration of the nonmodified peptide. Blocking the terminal amine group had thus a key role in protection of the tyrosyl residue. This finding might be exploited in the search for new pain inhibitors.
authors.affiliation: Laboratoire de Chimie Physique, UMR 8000 Université Paris Sud, F-91405 Orsay, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mozziconacci
authors.forename: Jacek
authors.initials: J
authors.lastname: Mirkowski
authors.forename: Filippo
authors.initials: F
authors.lastname: Rusconi
authors.forename: Pascal
authors.initials: P
authors.lastname: Pernot
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bobrowski
authors.forename: Chantal
authors.initials: C
authors.lastname: Houée-Levin
mesh_terms: D000588:Amines / Q000378:metabolism; D000838:Anions; D004744:Enkephalin, Methionine / Q000378:metabolism* / Q000528:radiation effects*; D005609:Free Radicals; D005720:Gamma Rays; D007700:Kinetics; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000588:Amines; D000838:Anions; D005609:Free Radicals; D013481:Superoxides; D004744:Enkephalin, Methionine