Alzheimer’s β-Amyloid: Insights into Fibril Formation and Structure from Congo Red Binding
We consider here the chemistry of Congo red (CR), its binding equilibrium to Alzheimer’s β-amyloid, and the kinetics of (3-amyioid formation. Spectroscopic UV/Vis measurements for the pH- and time-dependence binding of CR to Aβ analogues are analysed by Scatchard binding and the theory of nucleation-dependent fibril formation. CR likely binds electrostatically to the imidazolium sidechains of histidine residues that are exposed at the surface of amyloid fibrils. As revealed by atomic models of the Aβ protofilament, such as the nanotube β-helix and parallel β-sheet, the regular arrangement of histidines likely acts as a template for the end-to-end J-aggregation of CR molecules, which produces a red shift in UV/Vis absorption.
Key wordskinetics of amyloid aggregation histidine spectroscopy β-helix parallel β-sheet
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