Well-defined polymers with activated ester and protected aldehyde side chains for bio-functionalization

Polymers with reactive side chains and narrow molecular weight distributions were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, and the potential to utilize these polymers to prepare drug carriers was demonstrated. p-Nitrophenyl methacrylate (NPMA) and diethoxypropyl methacrylate (DEPMA) were polymerized utilizing cumyl dithiobenzoate (CDB) as the chain transfer agent and azobisisobutyronitrile (AIBN) as the initiator to high conversions (≥ 86%). The resulting pNPMA and pDEPMA had narrow molecular weight distributions (polydispersity indices < 1.3). The ability to functionalize these polymers was confirmed. For pNPMA, up to 86% of the side chains were substituted with the amino acid, glycine methyl ester. The side chains of pDEPMA were hydrolyzed to aldehydes and reaction with O-benzylhydroxylamine and O-methylhydroxylamine to form stable oxime bond conjugates was demonstrated. The percent substitution depended on the feed ratios. Conjugation of an aminooxy-functionalized RGD peptide was also demonstrated.