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Employing Unnatural Amino Acids to Develop Bioconjugations, Multivalent Conjugates, and Protein Modulation Strategies
King, Elizabeth
King, Elizabeth
Abstract
Unnatural amino acid technologies have been critical in introducing unique chemical functionality to proteins to allow for specific protein modulation or preparation of well-defined, homogeneous bioconjugates through bioconjugation chemistry. Bioconjugates are tremendously useful in disease treatment, diagnosis, and imaging. Therefore, the development and optimization of novel unnatural amino acids and bioconjugation methods, and their application to protein modulation or bioconjugate formation is a critical field of biochemical investigation. This thesis describes the development of a [2+2+2] cyclotrimerization bioconjugation using a novel unnatural amino acid. Then, several methods of preparing multivalent conjugates, which have a broader range of therapeutic applications than typical bivalent conjugates, are discussed. Finally, efforts to assay and modulate human protein arginine methyltransferase 1 using photoregulation unnatural amino acid technology are described. This thesis aims to expand the bioconjugation chemical toolbox, with high impact medicinal, therapeutic, and material applications.
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2020-05-01
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Chemistry