RESUMO
Polypeptides, especially star polypeptides, as a unique kind of biological macromolecules have broad applications in biomedical fields such as drug release, gene delivery, tissue engineering, and regenerative medicines due to their close structural similarity to naturally occurring peptides and proteins, biocompatibility, and amino acid functionality. However, the synthesis of star polypeptide mainly relies on the conventional primary amine-initiated ring-opening polymerization (ROP) of N-carboxyanhydrides (NCA) and suffers from low polymerization activity and limited controllability. This study proposes a fast, efficient and metal-free strategy to access star (co)polypeptides by combining the Michael reaction between acrylates and secondary aminoalcohols with the hydrogen-bonding organocatalytic ROP of NCA. This approach enables the preparation of a library of star (co)polypeptides with predesigned molecular weights, narrow molecular weight distributions, tunable arm number, and arm compositions. Importantly, this method exhibits high activity and selectivity at room temperature, making it both practical and versatile in synthesis applications.