Facile Synthesis of Helical Multiblock Copolypeptides: Minimal Side Reactions with Accelerated Polymerization of N‑Carboxyanhydrides

Multiblock copolypeptides have attracted broad interests because their potential to form ordered structures and possess protein-mimetic functions. Controlled synthesis of multiblock copolypeptides through the sequential addition of N-carboxyanhydrides (NCAs), especially with the block number higher than five, however, is challenging and rarely reported due to competing side reactions during the polymerization process. Herein, we report the unprecedented synthesis of block copolypeptides with up to 20 blocks, enabled by ultrafast polypeptide chain propagation in a water/chloroform emulsion system that outpaces side reactions and ensures high end-group fidelity. Well-defined multiblock copolypeptides with desired block numbers, block lengths, and block sequences, as well as very low dispersity were readily attainable in a few hours. This method paves the way for the fast production of a large number of sequence-regulated multiblock copolypeptide materials, which may exhibit interesting assembly behaviors and biomedical applications.