Date of Award
Doctor of Philosophy (PhD)
Chemistry & Biochemistry
Steven M. Pascal
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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Raut, Krishna K..
"Structural Insights into the cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, and Interaction With Cisplatin"
(2023). Doctor of Philosophy (PhD), Dissertation, Chemistry & Biochemistry, Old Dominion University, DOI: 10.25777/n7js-cb06