Synthesis of polypeptides via bioinspired polymerization of in situ purified N -carboxyanhydrides

Significance Biomacromolecules are synthesized in cells with high precision, although the cellular environment contains numerous molecules and species other than the building blocks. In contrast, even the state-of-the-art chemical synthesis of macromolecules is exclusively carried out under a specific condition containing only clean, essential starting materials to minimize side reactions. Inspired by ribozyme-catalyzed protein synthesis, we report here controlled polypeptide synthesis by nonpurified N -carboxyanhydride monomers in an oil/water biphasic system that mediates impurity segregation and enables very fast polymerization that outpaces competing side reactions.