Department or Program



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


Degree Name

Bachelor of Science

Number of Pages


Components of Thesis

1 pdf file


Available to all on Friday, May 05, 2028