Polyproline: A Synthetic Polypeptide With Unique Properties

Polyproline is a unique polypeptide defined by its unusual conformational rigidity and physicochemical behavior. Addressing long-standing challenges in its synthesis and characterization, this mini-review highlights recent advances in the ring-opening polymerization of proline N-carboxyanhydride (NCA), enabling the controlled and scalable preparation of well-defined polyproline architectures. These developments have unlocked diverse applications in advanced materials, including systems that exploit intrinsic thermoresponsive behavior arising from conformational transitions, leading to Lower Critical Solution Temperature (LCST)-type phase separation with pronounced hysteresis. Emerging applications span smart 3D printed hydrogels, nanoparticles, membrane-active materials, and polyproline-based conjugates, where polyproline serves as a biocompatible alternative to poly(ethylene glycol) (PEG). Collectively, these advances position polyproline as a promising platform in biomaterials, offering benefits such as enhanced stability, reduced immunogenicity, and expanded functional versatility.