Ring-opening polymerization of N-carboxyanhydrides: An efficient approach toward peptides, peptoids, and functional materials

Abstract

Polypeptides, as one of the most remarkable biomacromolecules in nature, possess immense application potential due to their protein-mimetic architectures. Since the discovery of N-carboxyanhydride (NCA) monomers in the early 20th century, these cyclic derivatives have revolutionized polypeptide synthesis by overcoming the inherent challenges in amino acid polycondensation. NCA remains an active research frontier in polymer science and materials engineering. In this review we critically summarize recent advances in NCA-based polymerization strategies. We first highlight ring-opening polymerization approaches, followed by an in-depth discussion on copolymerization systems with emphasis on monomer compatibility. As molecular assembly serves as the critical bridge connecting polymer synthesis to functional applications, we subsequently analyze various self-assembly mechanisms of NCA-derived polypeptides, with a focus on elucidating the driving forces underlying different supramolecular architectures. Furthermore, we comprehensively overview the emerging functional applications of these polypeptide materials across biomedical and nanotechnology domains. We critically analyze persistent challenges while charting emergent research frontiers in this field. This review not only consolidates the recent progress in NCA polymerization but also provides mechanistic insights into molecular assembly and a roadmap for advancing functional polypeptide materials in next-generation applications.