Interaction of Amyloid Aβ(9-16) Peptide Fragment with Metal Ions: CD, FT-IR, and Fluorescence Spectroscopic Studies

Heavy metal ions and those of aluminum may interact with amyloid-beta peptides (Alpha beta) associated with Alzheimer's disease, contributing to A beta aggregation and fibrillation that worsen this neuropathology. Nevertheless, the precise residues involved in metal ligation or interaction are yet to be established, although the N-terminal A beta(1-16) peptide fragment is considered to be the metal-binding domain. However, because the results of the metal ion binding studies using A beta(1-16) were not very conclusive, we have investigated shorter peptides. Here, we report the synthesis of truncated A beta(9-16) peptide of the human A beta(1-40) and A beta(1-42) peptides, as well as its characterization by nuclear magnetic resonance and mass spectrometry. Furthermore, the A beta(9-16) peptide interactions with various metal ions like Cu2+, Zn2+, Fe3+, Al3+, and Ni2+ were studied by circular dichroism, Fourier transform-infrared, and fluorescence spectroscopy. Our results show that the newly synthesized peptide sequence, which contains just two histidine and one tyrosine residues, seems to be a key site for metal binding, which was not thoroughly investigated so far. Light scattering spectra of A beta(9-16) and its complexes with metal ions were measured, whereas some fluorescence experiments were also performed. Our data suggest that A beta(9-16) peptide fragment coordination by metal ions is dependent on the type of metal, and the amino acid residues involved in metal bonding. [GRAPHICS] .