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 2 O 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 2 O 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.