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Development and Optimization of Bioconjugations to Probe and Modulate Protein Function
Travis, Christopher
Travis, Christopher
Abstract
Bioconjugate chemistry is a critical field with widespread applications to the visualization, diagnosis, and treatment of various diseases. Thus, it is crucial to investigate and optimize present bioconjugation methods, while continuing to develop novel bioconjugations to expand the scope of the field and provide numerous chemical tools for various applications. This thesis describes the development and optimization of bioconjugations using unnatural amino acid (UAA) technology to prepare homogenous, well-defined macromolecular complexes. First, the utilization of the Glaser-Hay bioconjugation to modulate protein function will be discussed. Next, an investigation into the aqueous Glaser-Hay reaction mechanism and subsequent optimization of the bioconjugation will be presented. A novel [2 + 2 + 2] cycloaddition bioconjugation reaction will then be presented, followed by efforts to generate a multivalent bioconjugate. Finally, efforts to assay and modulate the activity of Cas9 will be examined. This thesis aims to extend the chemical toolbox to probe and control biological systems, with applications in the fields of medicine and pharmaceuticals.
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2018-12-01
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Chemistry