Ambivalent role of ascorbic acid in the metal-catalyzed oxidation of oligopeptides.

Abstract The effect of ascorbic acid on the metal-catalyzed oxidation of a human prion protein model peptide has been studied. The complex formation of the peptide was clarified first. The studied model peptide contains a methionine and a histidine amino acids which are important both as binding sites for metal ions and sensitive parts of the protein for oxidation. pH-potentiometric, UV–Vis and circular dichroism spectroscopic techniques were applied to study the stoichiometry, stability and structure of the copper(II) complexes, while HPLC-MS and MS/MS were used for identifying the products of metal-catalyzed oxidation. 3N and 4N complexes with (Nim,N−,N−,S) and (Nim,N−,N−,N−) coordination modes are formed at pH 7.4, where the oxidation was studied. Singly, doubly and triply oxidized products are formed in which the methionine and/or the histidine side chain is oxidized. The oxidation was carried out with hydrogen peroxide solution by the addition of metal ions, namely copper(II) and iron(III) and/or ascorbic acid.