title: Prion-derived copper-binding peptide fragments catalyze the generation of superoxide anion in the presence of aromatic monoamines.
abstract: OBJECTIVE
  Studies have proposed two opposing roles for copper-bound forms of prion protein (PrP) as an anti-oxidant supporting the neuronal functions and as a pro-oxidant leading to neurodegenerative process involving the generation of reactive oxygen species. The aim of this study is to test the hypothesis in which putative copper-binding peptides derived from PrP function as possible catalysts for monoamine-dependent conversion of hydrogen peroxide to superoxide in vitro.
  
  
  METHODS
  Four peptides corresponding to the copper (II)-binding motifs in PrP were synthesized and used for analysis of peptide-catalyzed generation of superoxide in the presence of Cu (II) and other factors naturally present in the neuronal tissues.
  
  
  RESULTS
  Among the Cu-binding peptides tested, the amino acid sequence corresponding to the Cu-binding site in the helical region was shown to be the most active for superoxide generation in the presence of Cu(II), hydrogen peroxide and aromatic monoamines, known precursors or intermediates of neurotransmitters. Among monoamines tested, three compounds namely phenylethylamine, tyramine and benzylamine were shown to be good substrates for superoxide-generating reactions by the Cu-bound helical peptide.
  
  
  CONCLUSIONS
  Possible roles for these reactions in development of prion disease were suggested.
authors.affiliation: Graduate School of Environmental Engineering, The University of Kitakyushu, Kitakyushu 808-0135, Japan. kawanotom@env.kitakyu-u.ac.jp
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kawano
mesh_terms: D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011328:Prions / Q000737:chemistry*; D011485:Protein Binding; D013481:Superoxides / Q000737:chemistry*
chemical_list: D000588:Amines; D010446:Peptide Fragments; D011328:Prions; D013481:Superoxides; D003300:Copper