Department or Program
Chemistry
Abstract
Active DNA methylation is a dynamic epigenetic process that regulates local gene transcription, which not only determines cell fate, but also regulates a cell’s response to its environment. Within the hippocampal neurons, de novo DNA methyltransferases (DNMTs) catalyze the addition of a methyl group on cytosine creating 5-methylcytosine (5mC). The methylation is erased by the TET enzymes—a family of dioxygenases—by oxidizing the 5mC, quickly leading to base excision repair and the insertion of a new unalkylated cytosine. It has been established that knocking-out two of the three TET enzyme family members (TET1 and TET2) improves memory formation and stabilization, and therefore, the development of a class of small-molecule probes, called TET inhibitors, could be used therapeutically for conditions where memory is impaired, such as the rare autism-spectrum disorder, Pitt-Hopkins syndrome. In past studies, the cytosine-based TET Inhibitor, Bobcat339, was synthesized and found to inhibit both TET1 and TET2, but in order to be therapeutically effective, Bobcat339 had to be present in micromolar concentrations rather than the safer nanomolar concentration. A novel TET inhibitor has been synthesized, bearing resemblance to Bobcat339’s cytosine-based structure, but with the addition of more drug-like heterocycles. Data collected from ELISAs have indicated the novel TET inhibitor as an effective inhibitor of the TET enzyme.
Level of Access
Restricted: Embargoed [Open Access After Expiration]
First Advisor
Kennedy, Andrew
Date of Graduation
5-2023
Degree Name
Bachelor of Science
Recommended Citation
LaCroix, Elizabeth G., "The Synthesis of a Novel TET Inhibitor and its Inhibition of the TET Enzyme" (2023). Honors Theses. 438.
https://scarab.bates.edu/honorstheses/438
Number of Pages
137
Components of Thesis
1 pdf file