Undergraduate Honors Theses

Thesis Defended

Spring 2018

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Biochemistry

First Advisor

Robert Kuchta

Second Advisor

Liu Xuedong

Third Advisor

Levente Szentkirályi

Abstract

Science has failed those who die from the treatment of an illness rather than the illness itself. DNA nanomachines hold the promise of improving the site specificity of drug delivery, which can combat the toxicity of the drug to healthy cells and in turn, decrease unnecessary patient deaths due to treatment. We have found a novel synthesis pathway for a reversible redox- active nucleoside (n-nucleoside) that has the promise to be incorporated in and create redox- active DNA. Synthesis of 5’-deazalloxazine-ribonolactone was achieved via sodium hydride catalyzed glycosylation of 1-a-chloro-3,5-ditoluoyl-2-deoxy-D-ribose (5’,3’-protected-chloro- ribose). We were not able to reproduce results obtained by Wang & Rizzo that showed N-3-b selectively as the thermodynamically favored product using the Vorbrüggen glycosylation of alloxazine. Aspects that need to be further optimized in continuation of the sodium hydride pathway and future synthesis pathways for the n-nucleoside were found to be the stability of the glycosidic bond, 2’ position for use in phosphoramidite chemistry and leaving group reactivity at the C-1 glycosylation site. The N-3-b regioisomer will allow for the hydrogen bonding face to change and base pair either with adenine or the p-nucleotide when placed in an oxidizing or reducing environment. Through the synthesis of the redox-active n-nucleotide, the creation of autonomous DNA nanomachines for drug trafficking is one step closer to preventing unnecessary patient deaths.

Included in

Biochemistry Commons

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