title: Kinetic profile of amyloid formation in the presence of an aromatic inhibitor by nuclear magnetic resonance.
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.
authors.affiliation: Carlson School of Chemistry and Biochemistry, Clark University , 950 Main Street, Worcester, Massachusetts 01610, United States.
authors.forename: Gai
authors.initials: G
authors.lastname: Liu
authors.affiliation: Carlson School of Chemistry and Biochemistry, Clark University , 950 Main Street, Worcester, Massachusetts 01610, United States.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Gaines
authors.affiliation: Carlson School of Chemistry and Biochemistry, Clark University , 950 Main Street, Worcester, Massachusetts 01610, United States.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Robbins
authors.affiliation: Carlson School of Chemistry and Biochemistry, Clark University , 950 Main Street, Worcester, Massachusetts 01610, United States.
authors.forename: Noel D
authors.initials: ND
authors.lastname: Lazo
keywords: NMR; ThT fluorescence; amyloid; curcumin