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2012 ; 3
(10
): 856-9
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Kinetic profile of amyloid formation in the presence of an aromatic inhibitor by
nuclear magnetic resonance
#MMPMID24900390
Liu G
; Gaines JC
; Robbins KJ
; Lazo ND
ACS Med Chem Lett
2012[Oct]; 3
(10
): 856-9
PMID24900390
show ga
The self-assembly of amyloid proteins into ?-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 ?-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.