Date of Award

Fall 2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry & Biochemistry

Program/Concentration

Chemistry

Committee Director

Steven M. Pascal

Committee Member

Erin Purcell

Committee Member

Christopher Osgood

Committee Member

Stephen Beebe

Abstract

Cancer continues to be the leading global cause of death, with challenges in early diagnosis, drug resistance, non-specific drug targeting, and cancer recurrence and metastasis posing formidable obstacles in cancer therapy. In this context, Prostate Apoptosis Response-4 (Par-4), a pro-apoptotic tumor suppressor protein, emerged as a promising therapeutic target due to its ability to selectively induce apoptosis in cancer cells, thereby minimizing the drug-associated adverse effects. However, a comprehensive understanding of the structural features of Par-4, specifically the caspase-cleaved fragment (cl-Par-4), is crucial for therapeutic advancements.

This dissertation investigated the effects of various ions, both monovalent and divalent, on the conformational stability and solubility of cl-Par-4 under physiological conditions. By the use of several biophysical techniques including circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), UV-vis absorption spectroscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), our findings indicated that divalent cations, particularly Mg2+, can induce a structured conformation at significantly lower ionic concentrations (approximately five times lower concentrations) than monovalent cations (Na+ or K+). Anion identity was found to have a lesser influence than cation identity.

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DOI

10.25777/n7js-cb06

ISBN

9798381446609

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