Streamlined Synthesis of PEG-Polypeptides Directly from Amino Acids

The application of synthetic polypeptides is greatly limited by the difficulty of the purification and polymerization of N-carboxyanhydrides (NCAs). Here, we report a streamlined, controlled synthesis of polypeptides directly from amino acids, avoiding the NCA purification, by adding small-molecular amine scavengers (AS) in situ to efficiently eliminate the remaining organic impurities in the emulsion polymerization system. Such a process enables controlled synthesis of PEG-containing, homo, block, and random polypeptides in a highly consistent manner under open-air condition, directly from amino acid derivatives in various formats and independent of NCA preparation methods.