Direct electrochemical oxidation of amyloid-β peptides via tyrosine, histidine, and methionine residues

Abstract

The direct electrochemical oxidation of synthetic peptides analogous to the amyloid-beta (Aβ) implicated in the pathogenesis of Alzheimer's disease has been demonstrated on carbon screen-printed electrodes in the phosphate buffer (pH7.2) by using square wave voltammetry. The full-length peptide Aβ42 was found to produce two peaks at potentials of 0.6, 1.05, and a wave at about 1–1.5V (vs. Ag/AgCl) assigned, respectively, to its Tyr, His, and Met residues. The correspondence between the oxidation signals and the appropriate residues was established based on the analysis of voltammograms obtained for the free Tyr, His, and Met amino acids; for the Aβ16 peptide (representing the Aβ metal-binding domain and lacking the Met residue); for Aβ16 mutants differing in the number of His residues; and for the rat Aβ16 lacking the Tyr residue. The oxidation signals were found to be proportional to the amino acid and peptide concentrations. The observed difference in the electrochemical behavior of Aβ peptides widens the application of direct electrochemistry to peptide differentiation and point mutation studies as well as to investigation of Aβ aggregation and complexing with metal ions.