Copper‐Aβ Peptides and Oxidation of Catecholic Substrates: Reactivity and Endogenous Peptide Damage. Issue 47 (13th October 2016)

• Record Type: Journal Article
• Authors: Pirota, Valentina; Dell'Acqua, Simone; Monzani, Enrico; Nicolis, Stefania; Casella, Luigi
• Is Part Of: Chemistry. Volume 22:Issue 47(2016)
• Page Start: 16964
• Page End: 16973
• Publication Date: 2016-10-13
• Subjects: Alzheimer's disease -- Aβ peptides -- copper complexes -- dopamine -- oxidation; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201603824
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: The oxidative reactivity of copper complexes with Aβ peptides 1–16 and 1–28 (Aβ16 and Aβ28) against dopamine and related catechols under physiological conditions has been investigated in parallel with the competitive oxidative modification undergone by the peptides. It was found that both Aβ16 and Aβ28 markedly increase the oxidative reactivity of copper(II) towards the catechol compounds, up to a molar ratio of about 4:1 of peptide/copper(II). Copper redox cycling during the catalytic activity induces the competitive modification of the peptide at selected amino acid residues. The main modifications consist of oxidation of His13/14 to 2‐oxohistidine and Phe19/20 to ortho ‐tyrosine, and the formation of a covalent His6‐catechol adduct. Competition by the endogenous peptide is rather efficient, as approximately one peptide molecule is oxidized every 10 molecules of 4‐methylcatechol. Abstract : Competitive oxidative experiments with exogenous catechols show that copper complexes with both Aβ16 and Aβ28 peptides can significantly increase the oxidation rate of copper(II) towards the catechol compounds and promote endogenous peptide oxidation (see scheme). The main modifications consist of oxidation of His13/14 to 2‐oxohistidine and Phe19/20 to ortho ‐tyrosine, and the formation of a covalent His6‐catechol adduct.