Products of Cu(II)-catalyzed oxidation in the presence of hydrogen peroxide of the 1–10, 1–16 fragments of human and mouse β-amyloid peptide

Abstract

The interactions of proteins with reactive oxygen species (ROS) may result in covalent modifications of amino acid residues in proteins, formation of protein–protein cross-linkages, and oxidation of the protein backbone resulting in protein fragmentation. In an attempt to elucidate the products of the metal-catalyzed oxidation of the human ( H) and mouse ( M) (1–10 H), (1–10 M), (1–16 H) and (1–16 M) fragments of β-amyloid peptide, the high performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) methods and Cu(II)/H 2O 2 as a model oxidizing system were employed. Peptide solution (0.50 mM) was incubated at 37 °C for 24 h with metal:peptide:H 2O 2 molar ratio 1:1:1 for the (1–16 H), (1–16 M) fragments, and 1:1:2 for the (1–10 H), (1–10 M) peptides in phosphate buffer, pH 7.4. Oxidation targets for all peptide studied are the histidine residues coordinated to the metal ions. For the (1–16 H) peptide are likely His 13 and/or His 14, and for the (1–16 M) fragment His 6 and/or His 14, which are converted to 2-oxo-His. Metal-binding residue, the aspartic acid (D 1) undergoes the oxidative decarboxylation and deamination to pyruvate. The cleavages of the peptide bonds by either the diamide or α-amidation pathways were also observed.