The conjugation of polymers to therapeutically-useful proteins is an effective way to improve their stability as well as to protect them from degradation in vivo. These modifications ultimately increase circulation lifetime and bioavailability. Unfortunately, existing methods for the fabrication of such conjugates are ‘graft-to’ approaches that have considerable kinetic limitations. In this work, we describe the first modification of proteins via ‘graft-from’ ring-opening metathesis polymerization (ROMP) under physiological conditions. ROMP chemistry is extremely powerful due to its ability to quickly form low-dispersity polymers of targeted molecular weights and architectures, while being exceptionally tolerant of a variety of functional groups. A water-soluble ROMP ruthenium carbene catalyst was prepared and immobilized onto the protein surface to form a stable macroinitiator. This macroinitiator subsequently facilitated the growth of polymers directly from the protein surface resulting in high-molecular-weight protein:polymer conjugates. Finally, reactive block copolymers were grown from the protein surface and shown to react post-polymerzation to form fluorescent conjugates.

Protein:polymer conjugates via graft-from ring-opening metathesis polymerization

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.