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

Aleksandra Tobolska,Wojciech Wróblewski,Wojciech Bal,Nina E Wezynfeld,Urszula E Wawrzyniak

doi:10.1021/acs.inorgchem.1c03285

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.

Highlights

IntroductionMany of them, including amyloid-β (Aβ) related to Alzheimer’s disease, are rich in histidine (His) residues
Peptides and proteins are common and efficient metal-binding ligands
Most studies published in the literature have focused on the His-3 motif,[8] but the His-2 one could be even more appealing due to the labile coordination sites and, in consequence, the propensity to form ternary complexes.[9−13] This feature seems to be of great importance for selective recognition of biomolecules such as anions

Summary

Introduction

Many of them, including amyloid-β (Aβ) related to Alzheimer’s disease, are rich in histidine (His) residues The location of His residues in the peptide chain and the nature of the metal ion result in a variety of coordination properties and thermodynamic stabilities of the resulting chelates.[1] The presence of the His residue near the free N-terminus of peptides and proteins prompts high affinities of these ligands to transition-metal ions such as Cu(II) and Ni(II) through unique His-2 (XH) and His-3 (XZH) metal binding motifs (X stands for any amino acid residue and Z for any residue excluding Pro).[2,3] Peptides with these motifs have been employed in biological and medicinal applications, including copper sensing,[4] biomolecule (e.g., DNA) degradation,[5] biological imaging,[6] and ROS quenching.[7] Most studies published in the literature have focused on the His-3 motif,[8] but the His-2 one could be even more appealing due to the labile coordination sites and, in consequence, the propensity to form ternary complexes.[9−13] This feature seems to be of great importance for selective recognition of biomolecules such as anions

Methods

Results

Conclusion