Cu(II) Affinity for the Alzheimer’s Peptide: Tyrosine Fluorescence Studies Revisited

Copper­(II) binding to the amyloid-β peptide has been proposed to be a key event in the cascade leading to Alzheimer’s disease. As a direct consequence, the strength of the Cu­(II) to Aβ interaction, that is, the Cu­(II) affinity of Aβ, is a very important parameter to determine. Because Aβ peptide contain one Tyr fluorophore in its sequence and because Cu­(II) does quench Tyr fluorescence, fluorescence measurements appear to be a straightforward way to obtain this parameter. However, this proved to be wrong, mainly because of data misinterpretation in some previous studies that leads to a conflicting situation. In the present paper, we have investigated in details a large set of fluorescence data that were analyzed with a new method taking into account the presence of two Cu­(II) sites and the inner-filter effect. This leads to reinterpretation of the published data and to the determination of a unified affinity value in the 10¹⁰ M^–1 range