Link between Affinity and Cu(II) Binding Sites to Amyloid-beta Peptides Evaluated by a New Water-Soluble UV-Visible Ratiometric Dye with a Moderate Cu(II) Affinity

摘要

Being able to easily deter-mine the Cu(II) affinity for biomolecules of moderate affinity is important. Such biomolecules include amyloidogenic peptides, such as the well-known amyloid-beta peptide involved in Alzheimer's disease. Here, we report the synthesis of a new water-soluble ratiometric Cu(II) dye with a moderate affinity (10(9) M-1 at pH 7.1) and the characterizations of the Cu(II) corresponding complex by X-ray crystallography, EPR, and XAS spectroscopic methods. UV-vis competition was performed on the A beta peptide as well as on a wide series of modified peptides, leading to an affinity value of 1.6 X 10(9) M-1 at pH 7.1 for the A beta peptide and to a coordination model for the Cu(II) site within the A beta peptide that agrees with the one mostly accepted currently.