Synthesis and Characterization of Well-Defined PEGylated Polypeptoids as Protein-Resistant Polymers

Well-defined polypeptoids bearing oligomeric ethylene glycol side chains (PNMe(OEt)_nG, n = 1-3) with a controlled molecular weight (3.26-28.6 kg/mol) and narrow molecular weight distribution (polydispersity index, PDI = 1.03-1.10) have been synthesized by ring-opening polymerization of the corresponding N-carboxyanhydrides having oligomeric ethylene glycol side chains (Me(OEt)_n-NCA, n = 1-3) using primary amine initiators. Kinetic studies of polymerization revealed a first-order dependence on the monomer concentration, consistent with living polymerization. The obtained PEGylated polypeptoids are highly hydrophilic with good water solubility (>200 mg/mL) and are amorphous, with a glass transition temperature in the -41.1 to +46.4 °C range that increases with increasing molecular weight and decreasing side chain length. DLS and SANS analyses revealed no appreciable adsorption of lysozyme to PNMeOEtG. PNMeOEtG having different molecular weights exhibited minimal cytotoxicity toward HEp2 cells. These combined results suggest the potential use of PEGylated polypeptoids as protein-resistant materials in biomedical and biotechnological fields.