Ruthenium Substituted, NGR-Tagged Rubredoxin: A Potential Targeted Drug Therapy for Cancer

Date of Award

2021

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Francis E Jenney, Jr, PhD

Second Advisor

Kimberly Baker, PhD

Third Advisor

Valerie Cadet, PhD

Fourth Advisor

Lori Redmond, PhD

Abstract

Cancer is a set of more than 277 diseases that are characterized by abnormal cellular proliferation, replication, growth and migration. To date, it is the second leading cause of death in the United States of America. The most utilized treatments for cancer are surgery, radiation and chemotherapy. The challenges that these therapies pose to cancer patients are compromised immunity, frequent infections, degradation of healthy cells and nephrotoxicity. Even though these therapies show success limiting cancer growth, most of these side effects are due to the lack of specificity that these treatments have for cancer cells. Science continually investigates potential cancer therapies that will select for cancer cells without the destruction of healthy tissue. A potential method is the use of tumor homing peptides which are proteins that home to particular areas of vasculature. NGR homing peptide is shown to interact and bind to amino peptidase N (CD13) which is a receptor found on the cell membranes of certain cancer lines. Studies have shown that when NGR is conjugated with other biological agents or even chemotherapeutic agents, NGR selectively binds to CD13 and targets cancerous tissue, thus increasing the efficacy of treatment. Metallic compounds such as cisplatin and carboplatin have shown to be highly effective anti-cancer agents. Pyrococcus furious is a hyperthermophile that expresses rubredoxin, a small and stable non-heme metalloprotein. Research has shown rubredoxin’s iron core can be substituted with another metal like zinc, or nickel. Rubredoxin’s unique ability to unfold and re-fold, resuming its tertiary structure, makes it a valuable to medicinal research. It is hypothesized that if rubredoxin is substituted with a cytotoxic metal and modified to contain the NGR motif, the mutated rubredoxin can act as a targeted therapy for cancer.

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