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Amyloid Accelerators: Small Molecules that Accelerate Amyloid Formation by Amylin

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dc.contributor.advisor Raleigh, Daniel P en_US
dc.contributor.author Chen, Yuan en_US
dc.contributor.other Department of Chemistry. en_US
dc.date.accessioned 2017-09-20T16:51:58Z
dc.date.available 2017-09-20T16:51:58Z
dc.date.issued 2015-08-01 en_US
dc.identifier.uri http://hdl.handle.net/11401/77102 en_US
dc.description 90 pg. en_US
dc.description.abstract Amyloid formation in vivo plays a role in the pathology of more than 25 diseases. Amyloid formation by Islet Amyloid Polypeptide (IAPP) in the pancreas is a pathophysiological feature of type-2 diabetes. Much work has been performed in order to unravel the mechanisms of IAPP amyloid formation in vitro and recent studies suggest that toxic oligomers are generated during the formation of amyloids. Thus, it may be useful to look for compounds that accelerate fibril formation and reduce the lifetime of toxic intermediates. (S)-(+)-Flurbiprofen has been previously proven to accelerate IAPP amyloid formation. Computational simulation suggested the N-terminus of IAPP plays an important role in the interaction. In order to further understand the mechanism, the effect of (S)-(+)-Flurbiprofen were tested with different mutants of IAPP. The results suggest that the overall charge of IAPP is important in the interaction between negatively charged (S)-(+)-Flurbiprofen and positively charged IAPP. Moreover, a new compound, 4-[(4-chlorophenyl) thio] thiophene-3-carboxylic acid was identified and shown to accelerate amyloid formation by IAPP. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Chemistry en_US
dc.title Amyloid Accelerators: Small Molecules that Accelerate Amyloid Formation by Amylin en_US
dc.type Thesis en_US
dc.mimetype Application/PDF en_US
dc.contributor.committeemember Laughlin, Scott en_US
dc.contributor.committeemember Green, David. en_US

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