Type
Text
Type
Thesis
Advisor
Raleigh, Daniel P | Laughlin, Scott | Green, David.
Date
2015-08-01
Keywords
Chemistry
Department
Department of Chemistry.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/77102
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
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. | 90 pages
Recommended Citation
Chen, Yuan, "Amyloid Accelerators: Small Molecules that Accelerate Amyloid Formation by Amylin" (2015). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2939.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2939