title: Copper-Aβ Peptides and Oxidation of Catecholic Substrates: Reactivity and Endogenous Peptide Damage.
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.
authors.affiliation: Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100, Pavia, Italy.
authors.forename: Valentina
authors.identifier: http://orcid.org/0000-0002-6683-1726
authors.initials: V
authors.lastname: Pirota
authors.affiliation: Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100, Pavia, Italy.
authors.forename: Simone
authors.identifier: http://orcid.org/0000-0002-1231-4045
authors.initials: S
authors.lastname: Dell'Acqua
authors.affiliation: Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100, Pavia, Italy.
authors.forename: Enrico
authors.identifier: http://orcid.org/0000-0002-8791-6446
authors.initials: E
authors.lastname: Monzani
authors.affiliation: Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100, Pavia, Italy.
authors.forename: Stefania
authors.identifier: http://orcid.org/0000-0002-6618-7555
authors.initials: S
authors.lastname: Nicolis
authors.affiliation: Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100, Pavia, Italy.
authors.forename: Luigi
authors.identifier: http://orcid.org/0000-0002-7671-0506
authors.initials: L
authors.lastname: Casella
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002396:Catechols / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D056831:Coordination Complexes / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D007700:Kinetics; D010084:Oxidation-Reduction
chemical_list: D016229:Amyloid beta-Peptides; D002396:Catechols; D056831:Coordination Complexes; D003300:Copper
keywords: Alzheimer's disease; Aβ peptides; copper complexes; dopamine; oxidation