Chemistry

Kinetic profile of amyloid formation in the presence of an aromatic inhibitor by nuclear magnetic resonance

Document Type

Article

Abstract

The self-assembly of amyloid proteins into β-sheet rich assemblies is associated with human amyloidoses including Alzheimer's disease, Parkinson's disease, and type 2 diabetes. An attractive therapeutic strategy therefore is to develop small molecules that would inhibit protein self-assembly. Natural polyphenols are potential inhibitors of β-sheet formation. How these compounds affect the kinetics of self-assembly studied by thioflavin T (ThT) fluorescence is not understood primarily because their presence interferes with ThT fluorescence. Here, we show that by plotting peak intensities from nuclear magnetic resonance (NMR) against incubation time, kinetic profiles in the presence of the polyphenol can be obtained from which kinetic parameters of self-assembly can be easily determined. In applying this technique to the self-assembly of the islet amyloid polypeptide in the presence of curcumin, a biphenolic compound found in turmeric, we show that the kinetic profile is atypical in that it shows a prenucleation period during which there is no observable decrease in NMR peak intensities. © 2012 American Chemical Society.

Publication Title

ACS Medicinal Chemistry Letters

Publication Date

10-11-2012

Volume

3

Issue

10

First Page

856

Last Page

859

DOI

10.1021/ml300147m

Keywords

amyloid, curcumin, NMR, ThT fluorescence

Cross Post Location

Student Publications

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