A S-Sn Lewis Pair-Mediated Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydrides: Fast Kinetics, High Molecular Weight, and Facile Bioconjugation.

ABSTRACT

The rapid and controlled generation of polypeptides with ultrahigh molecular weight (MW) and well-defined chain end functionality has been a great challenge. To tackle this problem, we report here an initiation system based on a S-Sn Lewis pair, trimethylstannyl phenyl sulfide (PhS-SnMe3), for the ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCAs). This initiator displays a strong solvent effect, and can yield polypeptides with high MW (>1.0 × 105 g·mol-1) and low polydispersity index within a few hours. The MWs of the obtained polypeptides are strongly dependent on the THF/DMF ratio. The polymerization follows a typical first-order kinetic character with respect to the monomer concentration in mixed THF and DMF. Moreover, a highly reactive phenyl thioester is in situ generated at the C-terminus of the polypeptides, which is readily accessible for native chemical ligation affording high MW and site-specific protein-polypeptide conjugates. Together, this initiator sheds light on regulating the ROP of NCAs via appropriate Lewis pair and solvent selection, and is particularly useful in preparing ultrahigh MW polypeptides within a short period of time.