Branched Polymer−Protein Conjugates Made From Mid-Chain-Functional P(HPMA)

A novel midchain-functional chain transfer agent was synthesized and used as a reversible addition-fragmentation chain transfer polymerization agent to prepare branched poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA). The P(HPMA) contained a thio-reactive group, namely, pyridyldisulfide midchain. The synthesized polymers were fully analyzed by (1)H NMR, GPC, and hydrolysis, confirming well-defined structures (predesigned molecular weights, narrow polydispersities, and high functionalization efficiencies). These midfunctionalized polymers were incubated with bovine serum albumin to generate protein-polymer conjugates. This straightforward methodology for the synthesis of branched midfunctionalized polymers for protein conjugation has the potential to enhance the properties of polymer-protein conjugates by improving biomolecule stability and enhancing circulation time.