Biomedical Engineering ETDs

Publication Date

Spring 5-15-2020

Abstract

Abnormal functioning of small GTPases is implicated in a variety of diseases, ranging from neurological and developmental diseases to cancer. In fact, mutant GTPases are found in up to 30% of cancers. Thus, small GTPases are a highly relevant target in drug discovery and development. High-throughput targeted screening of small molecules is the most productive method of discovering compounds that can give insights into drug development. This thesis describes improvements made to a high-throughput GTPase-targeted screening method to minimize confounding systematic error. It also describes the follow-up characterization of a compound that was identified in a high-throughput screen. The compound under investigation, PR-619, was shown to be a pan-GTPase inhibitor that competitively inhibits guanine nucleotide binding in a panel of sixteen members of the Ras superfamily of small GTPases. Additionally, PR-619 was demonstrated to inhibit GTPase-effector interaction and to produce effects in cellular studies.

Language

English

Keywords

GTPase, inhibitor, competitive, high throughput screening, drug discovery, multiplex

Document Type

Thesis

Degree Name

Biomedical Engineering

Level of Degree

Masters

Department Name

Biomedical Engineering

First Committee Member (Chair)

Dr. Larry A. Sklar

Second Committee Member

Dr. Steven Graves

Third Committee Member

Dr. Andrew Shreve

Fourth Committee Member

Dr. Angela Wandinger-Ness

Available for download on Sunday, July 31, 2022

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