Glycopolypeptoids as Novel Biomimetic Antifreeze Agents: Structural Design, Synthesis, and Antifreeze Properties.

Glycopolypeptoids were synthesized and showed effective antifreeze activity, demonstrating their potential as novel antifreeze agents for cryopreservation. These polypeptide analogs offer improved stability and tunability compared with natural antifreeze glycoproteins (AFGPs) and existing synthetic mimics. Using the ring-opening polymerization of N-substituted N-carboxyanhydride monomers followed by click chemistry, glycopolypeptoids with controlled polymerization degrees and varied structures were designed and prepared. Their antifreeze performance was assessed via nanoliter osmometry and ice recrystallization inhibition assays, revealing a strong correlation between the molecular structure and antifreeze activity. The findings highlight glycopolypeptoids as a promising, cost-effective alternative to natural AFGPs, providing new insights into the development of biomimetic cryoprotectants. This study expands the understanding of synthetic antifreeze materials and offers a practical approach for improving cryopreservation efficiency in biomedical and industrial applications.