Interactions of Copper(ii) and Zinc(ii) Ions with the Peptide Fragments of Proteins Related to Neurodegenerative Disorders: Similarities and Differences.

Metal binding ability and coordination modes of the copper(II) and zinc(II) complexes of various peptide fragments of prion, amyloid-β, and tau proteins, are summarized in this review. Imidazole-N donors are the primary metal binding sites of all three proteins, but the difference in the location of these residues and the presence or absence of other coordinating side chains result in significant differences in the complex formation processes. The presence of macrochelates and the possibility of forming multicopper complexes are the most important characteristic of prion fragments. Amyloid-β can form highly stable complexes with both copper(II) and zinc(II) ions, but the preferred binding sites are different for the two metal ions. Similar observations are obtained for the tau fragments, but the metal ion selectivity of the various fragments is even more pronounced. In addition to the complex formation, copper(II) ions can play an important role in the various oxidative reactions of peptides. Results of the metal ion-catalyzed oxidation of peptide fragments of prion, amyloid-β, and tau proteins are also summarized. Amino acid side chain oxidation (mostly methionine, histidine and aspartic acid) and protein fragmentations are the most common consequences of this process.