Stabilization of Proteins by Polymer Conjugation via ATRP

摘要

US Army Research Office has funded this 2-year basic research effort by ICx-Agentase to study new techniques of modifying native enzymes with polymers via atom transfer radical polymerization to increase their solubility and utility in organic solvents and to increase their stability in body. Protein-initiated ATRP would enable us to overcome many problems in conventional technology that modifies proteins with polyethylene glycol or 'pegylation'. These problems include lack of control on number of polymer chains attached per protein, low yield, tedious purifications, and less-than- optimal stabilization. The first goal of this study is to develop new technique/s to modify enzymes with hydrophobic polymers and dissolve high concentrations of modified enzymes in organic solvent and apply them in self decontaminating paints and coatings. The second goal of the study was to study the potential of using of ATRP modified proteins for therapeutic applications in vivo. Chymotrypsin and BChE conjugates synthesized by ATRP were demonstrated and were highly active and much more stable in mouse serum as compared to conventionally pegylated enzymes.