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Utilization of Unnatural Amino Acids in the Development of Novel Functions and Probing Applications

Russell, Brent
Abstract
The utilization of unnatural amino acids opens the door for thousands of ways to expand the chemical diversity of proteins, providing functional groups for chemical manipulation that would otherwise be impossible. The ability to site-specifically incorporate unnatural amino acids confers a degree of control and specificity over these reactions that allows for precision probing and engineering of pathways and functions. A number of these chemical possibilities will be explored in this thesis. The utilization of fluorotyrosines in green fluorescent protein marks the first step towards developing a novel, physiologically relevant fluorescent biosensor. The use of unnatural amino acids in Utag, a medically relevant enzyme, allows for the exploration of the utility of fluorescent bioconjugations in developing a noninvasive screen for prostate cancer. Finally, the unique radical pathway of a multifunctional globin, dehaloperoxidase, will be explored via the utilization of 3-fluorotyrosine. In short, unnatural amino acids allow for the exploration and development of novel reactions and applications of proteins that have before been out of reach.
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2019-04-01
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Neuroscience
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