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

通过具有中等 Cu(II) 亲和力的新型水溶性紫外-可见比率染料评估亲和力与 Cu(II) 与淀粉样β肽结合位点之间的联系

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作者:Amandine Conte-Daban, Valentina Borghesani, Stéphanie Sayen, Emmanuel Guillon, Yves Journaux, Geoffrey Gontard, Laurent Lisnard, Christelle Hureau

Abstract

Being able to easily determine the Cu(II) affinity for biomolecules of moderate affinity is important. Such biomolecules include amyloidogenic peptides, such as the well-known amyloid-β peptide involved in Alzheimer's disease. Here, we report the synthesis of a new water-soluble ratiometric Cu(II) dye with a moderate affinity (109 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 Aβ peptide as well as on a wide series of modified peptides, leading to an affinity value of 1.6 × 109 M-1 at pH 7.1 for the Aβ peptide and to a coordination model for the Cu(II) site within the Aβ peptide that agrees with the one mostly accepted currently.

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