Electrochemical Analysis of Amyloid-β Domain 1-16 Isoforms and Their Complexes with Zn(II) Ions

•The Tyr based Aβ16 oxidation signal is sensitive to amino acid substitution and modification.•Effects of Zn(II) ions on Aβ16 isoforms’ oxidation are registered at pH 5.5–9.•H6A-H13A-Aβ16 is differed in its behavior vs. Aβ16 compared to other isoforms.

Tyrosine based electrochemical analysis of various isoforms of the amyloid-β fragment 1-16 (Aβ16), representing the metal-binding domain of Alzheimer’s human Aβ peptide with amino acid substitutions and post-translational modification (D7H, D7N, H6R, H6A-H13A, E11K, and pS8), was carried out by square wave voltammetry on carbon screen printed electrodes. Electrochemical analysis allowed for distinguishing: (i) some isoforms under study from the “normal variant” of the Aβ16; and (ii) the isoforms from one another. Effects of Zn(II) ions on Aβ16 isoforms’ oxidation were studied within a wide range of Zn(II) ion concentrations in HEPES-buffers with the pH values of 5.5 to 9. Except for H6A-H13A-Aβ16, addition of Zn(II) ions significantly reduced the intensity of oxidation signals for Aβ16 and its isoforms and shifted the peaks to the more positive potentials. H6A-H13A-Aβ16 demonstrated distinctly different electrochemical behavior both in the absence and presence of Zn(II) ions. The observed effects were discussed in the light of known modes of the Zn(II) ions binding to Aβ16 and its isoforms. The proposed electrochemical assay based on the direct oxidation signal of a tyrosine residue emerges as a very promising tool for monitoring the conformational changes of Aβ peptides in vitro as well as for studying the effects of point mutations and amino acid modifications on the conformation of peptide-metal ion complexes.