Undergraduate Honors Theses

Thesis Defended

Summer 2015

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Biochemistry

First Advisor

Dr. Tad Koch

Second Advisor

Dr. Joseph Falke

Third Advisor

Dr. Gia Voeltz

Abstract

Chemotherapeutic prodrugs have demonstrated success in killing cancer cells; however they also pose harm to healthy cells. The objective of this project was to synthesize an improved prodrug that is selectively activated only in the cancer microenvironment, thus minimally affecting healthy tissue. A photolabile linker was hypothesized to achieve said objective. The Yin group discovered that the MARCKS-ED peptide can localize to the exosome via curvature sensing and electrostatic interactions. In addition, the Koch group determined that Doxazolidine (Doxaz) is more cytotoxic than its clinical drug precursor. Also, no cancer cell lines have shown resistance to this anthracycline. Based on these studies, we decided to synthesize a prodrug containing a photolabile linker, MARCKS-ED peptide, and the Doxaz anthracycline. We hypothesized that a specific sequence of synthesis and purification steps would generate the prodrug. I carried out steps and characterized the products using NMR, HPLC and ESI-MS+. The results confirmed that the desired product was produced. Preliminary in-vitro experiments also showed that the prodrug was endocytosed by cells. It was then predicted that application of UV light will activate the prodrug and cause cell death.