Presenter: Sydney Nicole Tor
Faculty Sponsor: Todd Emrick
School: UMass Amherst
Research Area: Chemistry and Materials Science
Session: Poster Session 4, 2:15 PM - 3:00 PM, Auditorium, A34
ABSTRACT
The covalent attachment of polymers to therapeutic proteins enhances their efficacy and holds promise for improving targeting. For example, polyethylene glycol (PEG)-protein bioconjugates are found to prolong in vivo circulation half-life by increasing the hydrodynamic radius of the protein, thus reducing the necessary dosing frequency. However, emerging data suggests an acquired immune response associated with PEG. Moreover, PEGylation reagents lack site specificity, leading to low yields and laborious separations. Our studies on polymer zwitterionic hold promise as therapeutic biomaterials due to their extensive hydrophilicity combined with their low immunogenicity, and the exceptional potential for structure functionalization. This presentation will focus on a novel enzyme-induced bioconjugation method, using the enzyme tyrosinase, implemented for high site specificity and versatility. The protein selected was Bovine Serum Albumin (BSA), due to its role in blood plasma production and cost- effectiveness. BSA contains a single surface thiol far from its active sites. Poly(2- methacryloyloxyethyl phosphorylcholine) (PMPC)-based copolymers were synthesized using RAFT polymerization, to produce structures with pendant phenols. In aqueous buffer, tyrosinase oxidizes the phenolic groups, increasing their electrophilicity towards free thiols to yield protein-zwitterion conjugates. The advantages of this method are compared to the synthesis and conjugation of pentafluorophenyl ester-terminated- poly(MPC), which reacts with amines on protein surfaces. The polymers used in bioconjugation are tested in vitro with healthy and cancerous human cells in cytotoxicity assays. The greater goal is to implement this coupling method to attach functional polymer zwitterions to therapeutic antibodies, creating new types of antibody-polymer-drug conjugates (APDCs).
