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Design and Synthesis of Sulfonated Polymers for the Preparation of Polymer-protein Conjugates with Improved Therapeutic Abilities and Mechanistic Studies

Abstract

In the first part of this thesis is described the use of free radical polymerization to synthesize a variety of sulfonated polymers. These polymers were employed in a biological screening study to determine their ability to participate in binding of basic fibroblast growth factor to its cellular receptor. Preliminary data suggests that poly(sodium vinyl sulfonate) (pVS) best serves this role. In order to obtain end-functionalized polymers with narrow molecular weight distribution profiles, controlled polymerizations of this monomer using reversible addition-fragmentation chain transfer (RAFT) were attempted. In addition, RAFT polymerization was used to synthesize poly(poly(ethylene glycol methyl ether acrylate)) (pPEGA) and poly(sodium styrene sulfonate)-co-poly(poly(ethylene glycol methacrylate)) (pSS-co-PEGMA). In the second part of this thesis, attempts to prepare fluorescent protein-polymer conjugates for use in biological mechanism studies are described. To achieve this, post-polymerization modification and fluorescent chain transfer agent (CTA) methodologies were employed to install a fluorescent tags onto these polymers.

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