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
Repository Citation
Liu, Gai; Gaines, Jennifer C.; Robbins, Kevin J.; and Lazo, Noel D., "Kinetic profile of amyloid formation in the presence of an aromatic inhibitor by nuclear magnetic resonance" (2012). Chemistry. 131.
https://commons.clarku.edu/chemistry/131
Cross Post Location
Student Publications