Date of Award

Spring 2026

Degree Type

Thesis

Department

College of Pharmacy

Director of Thesis

Douglas Pittman

Second Reader

Michael Wyatt

Abstract

Protein-protein interactions are important targets in cancer biology as they can make historically “undruggable” proteins viable drug targets. However, the current approach to targeting protein-protein interactions relies on the use of small molecule drugs, which have low efficiencies as they must cover a large surface area of the interaction. Further, traditional drug therapies often lead to off-target toxicity, limiting therapeutic specificity. The objective of this project is to develop a selection system in yeast to identify short peptide sequences that can disrupt protein-protein interactions specific to cancer cells. Following proof of principle and development of the AH109 yeast strain having a new reporter gene, an oligo/peptide library will be generated to develop a high-throughput selection for disruption of any combination of protein interactions. Promising candidates will be converted into peptide-mimetic compounds. Inhibitory drug-like compounds will then be optimized into pharmaceutically relevant molecules with REPLACE (Replacement with Partial Ligand Alternatives through Computational Enrichment) technology.

First Page

1

Last Page

30

Rights

© 2026, Chesley C. Blake

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