Polypeptide Synthesis
Polypeptides, sharing the same backbone as natural proteins, are widely utilized in the biomedical field due to their exceptional biological properties. Ring-opening polymerization (ROP) of N-carboxyanhydride (NCA) serves as one of the primary strategies for synthesizing polypeptide materials with high molecular weights and well-defined structures. Building on extensive studies of NCA ROP, we have uncovered the unique mechanism of α-helix-inducing autocatalysis and developed the nature-inspired cooperative covalent polymerization (CCP) strategy. This innovative approach dramatically accelerates polymerization rates by 2–3 orders of magnitude compared to conventional methods. The ultrafast polymerization suppressed the side reactions and thus eliminated the dependence on strictly anhydrous conditions, ultrapure NCA monomers, and expensive catalysts. This breakthrough facilitates the large-scale production of well-defined polypeptide biomaterials with minimized technical barriers. Further investigations into the mechanism and methodology will not only advance the development of high-performance polypeptide biomaterials but also provide new insights into fundamental biochemical questions, including the origin and evolution of natural proteins.
In Vivo/Click chemistry
Bioorthogonal chemistry is a strategy for performing chemical reactions within living systems. It involves reactions that are unrelated to other natural progresses in the organism, allowing for selective labeling, detection, and manipulation of specific molecules or processes. We are committed to the development of novel bioorthogonal chemistry and performing different reactions in this lab ranging from azide-alkyne cycloaddition, hydroxylamine-mediated reactions, affinity labeling, and photoconversion chemistry. These methods are powerful tools for studying chemical processes and molecular functions in biology, especially in the area of large molecules engineering on cell surface via natural metabolic pathway.
Gene Delivery
Polypeptides were among the first materials explored as nonviral gene delivery vectors due to their biocompatibility and functional versatility. We developed a library of cationic α-helical polypeptides with cell-penetrating peptide (CPP)-like properties using the precise ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs). These polypeptides demonstrated the ability to effectively disrupt endosomes, a critical step for successful gene delivery, facilitating efficient intracellular release of genetic material. Our studies confirmed their robust performance in both in vitro and in vivo systems, achieving high transfection efficiency with mild cytotoxicity. These findings highlight the potential of cationic α-helical polypeptides as a promising platform for safe and effective nonviral gene delivery in gene therapy applications.
