Linking catalysis with functionality expansion: the way toward polypeptide-based hybrid materials from accelerated polymerizations

Synthetic polypeptides derived from N-carboxyanhydride ring-opening polymerization (NCA-ROP) hold immense potential as biomaterials, yet their inability to fully replicate the structural and functional complexity of natural peptides and proteins remains a critical limitation. This perspective proposes that catalysis-driven NCA-ROPs, including those promoted by exogeneous catalysts or their very products, offer a route to bypass the inherent challenge of sequence control by transforming the product polypeptides into functional hybrid materials. A few examples are given in the article to show that catalytic methodologies not only enhance polymerization kinetics, but also empower the seamless fusion of polypeptides with proteins, nanomaterials, inorganic matrices and others. For instance, metal–organic framework (MOF)-catalyzed NCA-ROP enables one-pot synthesis of hybrid nanocatalysts, while water-assisted, protein-initiated polymerization produces therapeutic conjugates with better pharmacokinetic profile. By decoupling functionality tuning and diversification from precise sequence control and turning to the material hybridization approach, one may leverage polypeptides’ tunable secondary structures, degradability, and biocompatibility to build materials with emergent properties, such as composites for bone-tissue engineering and poly(ethylene glycol) (PEG) alternatives. Specifically, revisiting polypeptide functionalization and surface-initiated polymerization may be necessary to attract more interest among researchers in different fields, and to promote polypeptides as versatile components in next-generation hybrid platforms.