Tuning Receptor Properties of Metal-Amyloid Beta Complexes. Studies on the Interaction between Ni(II)-Aβ_5-9 and...

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, Aβ_5-9, 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)-Aβ_5-9 complex and phosphate species result in significant changes in the Ni(II) oxidation signal. Thus, the Ni(II)-Aβ_5-9 complex could potentially serve as a receptor in electrochemical biosensors for phosphate species. The obtained results could also be important for nickel toxicology.