Protein-Polymer Conjugates via Graft-From Ring-Opening Metathesis Polymerization

by SERGEY A. ISAROV Protein therapeutics and biopharmaceuticals are used in a wide variety of clinical applications such as drug delivery and diagnostics. Unfortunately, protein-based therapies possess significant limitations as a result of degradative processes that restrict the lifetime of proteins in vivo. This project explores the growth of conformationally rigid polymers derived via graft-from ring-opening metathesis polymerization (ROMP) directly from the surface of proteins. We predict that these polymers can protect proteins from degradation, while bearing useful functionalities to improve their utility and behavior within biological systems. We report a novel aqueous ROMP technique for the growth of polymers from the surface of lysozyme. This technique represents the first example of the use of ROMP for the growth of polymers directly from the surface of a biological substrate under physiological conditions. Via extensive proof-of-concept studies, we report the successful formation of a protein ROMP macroinitiator that subsequently facilitated graft-from ROMP to afford protein-polymer conjugates of high molecular weights. Further optimization of reaction conditions will be performed in order to more precisely control polymer length, composition, and polymerization kinetics. Future studies will investigate ROMP from the surface of tobacco mosaic virus (TMV) to form high aspect ratio nanoparticle conjugates.