By attaching polymers to specific sites along a protein, bioconjugation presents an opportunity to increase the functionality of proteins. Bioconjugates have exhibited greater thermal and chemical stability, substrate affinity, and serum half-life. By adding two different polymers to a protein, bifunctional bioconjugation allows for greater control over the functionality of the protein, increasing the stability and efficiency of proteins for medicinal and industrial applications. In this project, an orthogonal photochemical strategy for the synthesis of bifunctional bioconjugates was performed on a mutant of ubiquitin with a cysteine residue at the C-terminus (77C-Ub). The major synthetic methods include atom transfer radical polymerization (ATRP) on free amines and reverse addition-fragmentation chain-transfer polymerization (RAFT) on the mutated cysteine residue. Both of these polymerizations use a ‘grafting-from’ approach, allowing for precise control over the site-specificity of the reactions. These orthogonal chemical strategies allow for the synthesis of well-defined polymers with a dispersity of less than 1.5 for both reactions. By characterizing each stage of the synthesis, this project presents a detailed, orthogonal strategy for the synthesis of well-defined bifunctional bioconjugates.
Authors: Ryan Parnell
Faculty Advisors: Kevin Burridge, Dominik Konkolewicz and Richard C. Page, Department of Chemistry and Biochemistry
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