Numerous conflicting values have been proposed regarding the affinity of Cu2+ for amyloid- (A) peptide, the causative agent of Alzheimer’s disease. In the present review, we critically compare the two approaches employed so far (the Kd and the stability constant approach) to express the affinity of copper( II) for the amyloid- (A) peptide and highlight the limits and the advantages of the two approaches. We also analyze the conditions employed for some experiments, which we have taken as examples, highlighting some of the points that may have generated the deriving divergent propositions. Through the analysis of the species distribution, we show the implications that a correct speciation may have on data interpretation as well as on experiment planning. By doing so, this review aims at shifting the perspective on the binding issue from the classic Kd approach, based on low and high affinity binding sites – often referred to as component I and II, or form I and II – to stoichiometry determination and, as a consequence, to the speciation of Cu–A complexes. Additionally, this review has the purpose of demonstrating that a quantitative assessment of the coordination sphere is complicated by the variety of equilibria often occurring over a relatively narrow pH range.
|Titolo:||Copper(II) interaction with amyloid-β: Affinity and speciation|
|Data di pubblicazione:||2012|
|Appare nelle tipologie:||1.1 Articolo in rivista|