Date Approved

5-18-2023

Embargo Period

5-22-2023

Document Type

Thesis

Degree Name

M.S. Pharmaceutical Sciences

Department

Chemistry and Biochemistry

College

College of Science & Mathematics

Advisor

Venkatesh V. Nemmara, Ph.D.

Committee Member 1

K. Ramanujam Chary, Ph.D.

Committee Member 2

Subash Jonnalagadda, Ph.D.

Subject(s)

Polyamines; Biochemistry

Disciplines

Medicinal-Pharmaceutical Chemistry | Physical Sciences and Mathematics

Abstract

Polyamines such as putrescine, spermidine, and spermine modulate critical cellular processes, including gene expression and cell proliferation. Cellular polyamine regulation is a complex mechanism controlled by three different proteins: Ornithine decarboxylase (ODC), Antizyme (OAZ), and Antizyme Inhibitor (AZIN). While ODC is directly involved in polyamine biosynthesis, OAZ, and AZIN regulate the ODC activity via protein-protein interactions. The dysregulation of ODC, OAZ, and AZIN leads to elevated polyamines in numerous pathologies, making them attractive targets for controlling polyamine levels. Besides regulating polyamine synthesis, OAZ modulates polyamine transport. However, the precise mechanism remains elusive. In this research, we discuss our approach to bridging the current knowledge gap on polyamine regulators. Furthermore, we will highlight our chemical strategies to elucidate the functional impacts of protein polyamination.

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