Tuning Receptor Properties of Metal–Amyloid Beta Complexes. Studies on the Interaction between Ni(II)–Aβ5–9 and Phosphates/Nucleotides

Abstract

Amyloid-beta (Aβ) peptides, potentially relevant in the pathology of Alzheimer’s disease, possess distinctive coordination properties, enabling an effective binding of transition-metal ions, with a preference for Cu(II). In this work, we found that a N-truncated Aβ analogue bearing a His-2 motif, Aβ5–9, forms a stable Ni(II) high-spin octahedral complex at a physiological pH of 7.4 with labile coordination sites and facilitates ternary interactions with phosphates and nucleotides. As the pH increased above 9, a spin transition from a high-spin to a low-spin square-planar Ni(II) complex was observed. Employing electrochemical techniques, we showed that interactions between the binary Ni(II)–Aβ5–9 complex and phosphate species result in significant changes in the Ni(II) oxidation signal. Thus, the Ni(II)–Aβ5–9 complex could potentially serve as a receptor in electrochemical biosensors for phosphate species. The obtained results could also be important for nickel toxicology.