Oxidase Reactivity of CuII Bound to N-Truncated Aβ Peptides Promoted by Dopamine |
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Authors: | Chiara Bacchella Simone DellAcqua Stefania Nicolis Enrico Monzani Luigi Casella |
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Affiliation: | Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100 Pavia, Italy; (C.B.); (S.D.); (S.N.); (E.M.) |
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Abstract: | The redox chemistry of copper(II) is strongly modulated by the coordination to amyloid-β peptides and by the stability of the resulting complexes. Amino-terminal copper and nickel binding motifs (ATCUN) identified in truncated Aβ sequences starting with Phe4 show very high affinity for copper(II) ions. Herein, we study the oxidase activity of Cu–Aβ4−x] and Cu–Aβ1−x] complexes toward dopamine and other catechols. The results show that the CuII–ATCUN site is not redox-inert; the reduction of the metal is induced by coordination of catechol to the metal and occurs through an inner sphere reaction. The generation of a ternary CuII–Aβ–catechol] species determines the efficiency of the oxidation, although the reaction rate is ruled by reoxidation of the CuI complex. In addition to the N-terminal coordination site, the two vicinal histidines, His13 and His14, provide a second Cu-binding motif. Catechol oxidation studies together with structural insight from the mixed dinuclear complexes Ni/Cu–Aβ4−x reveal that the His-tandem is able to bind CuII ions independently of the ATCUN site, but the N-terminal metal complexation reduces the conformational mobility of the peptide chain, preventing the binding and oxidative reactivity toward catechol of CuII bound to the secondary site. |
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Keywords: | copper amyloid-β peptides Alzheimer’ s disease oxidative stress dopamine neurodegeneration |
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