Date

2017

Department or Program

Chemistry

Primary Wellesley Thesis Advisor

Professor David R. Haines

Abstract

Type II diabetes is a disease that begins as insulin resistance in the tissues of the body and over time, the insulin-producing β cells in the pancreas become so stressed that they cannot adequately produce insulin. Decreased β cell functionality leads to states of hyperglycemia where blood glucose levels are dangerously high, leading to complications such as heart attack and stroke. In order to develop treatments for this disease, the glucagon-like peptide-1 receptor (GLP-1R) has been identified as a medicinal target. Studies of the binding of GLP-1R have taken many directions, including X-ray crystallography and computational modeling. Also, peptide-based treatments for type II diabetes have been proposed and are in use. However, small molecules can aid both fronts as treatments for type II diabetes and probes for small molecule active site exploration in GLP-1R. One particular small molecule that interacts with GLP-1R is T-0632. This molecule was originally developed for interacting with the cholecystokinin receptor, but it also binds well to GLP-1R. Although an antagonist to GLP-1R, T-0632 can be used to study the small molecule binding site of GLP-1R to give insight into what small molecule structures could activate the receptor. Our research focuses on synthesizing photolabile T-0632 derivatives to map the small molecule active site of GLP-1R with the help of our collaborators at the Mayo Clinic in Phoenix, AZ.

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