Journal
BIOCHEMISTRY
Volume 55, Issue 31, Pages 4255-4258Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biochem.6b00578
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Funding
- Virginia Tech new faculty start-up funds
- U.S. Department of Agriculture [VA-135992]
- Alzheimer's and Related Diseases Research Award Fund of the Virginia Center on Aging [16-1]
- Diabetes Action Research and Education Foundation
- Virginia Tech Center for Drug Discovery
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Amyloid formation of the 37-residue amylin is involved in the pathogenesis of type 2 diabetes and, potentially, diabetes-induced neurological deficits. Numerous flavonoids exhibit inhibitory effects against amylin amyloidosis, but the mechanisms of inhibition remain unclear. Screening a library of natural compounds uncovered a potent lead compound, the flavone baicalein. Baicalein inhibits amylin amyloid formation and reduces amylin-induced cytotoxicity. Analogue analyses demonstrated, for the first time, key roles of the vicinal hydroxyl groups on the A-ring. We provided mass spectrometric evidence that incubating baicalein and amylin leads to their conjugation, consistent with a Schiff base mechanism.
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