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 10(10) M(-1) range.