Synthetic antifreeze glycoproteins with potent ice-binding activity

Antifreeze glycoproteins (AFGPs) are produced by extremophiles to defend against tissue damage in freezing climates. Cumbersome isolation from polar fish has limited probing AFGP molecular mechanisms of action and limited developing bioinspired cryoprotectants for application in agriculture, foods, coatings, and biomedicine. Here, we present a rapid, scalable, and tunable route to synthetic AFGPs (sAFGPs) using N -carboxyanhydride polymerization. Our materials are the first mimics to harness the molecular size, chemical motifs, and long-range conformation of native AFGPs. We found that ice-shaping and ice-recrystallization inhibition activity increases with chain length and Ala is a key residue. Glycan structure had only minor effects and all glycans examined displayed antifreeze activity. The sAFGPs are biodegradable, non-toxic, and internalized into endocytosing cells. sAFGPs were found to be bystanders in cryopreservation of human red blood cells. Overall, our sAFGPs functioned as surrogates for bona fide AFGPs, solving a long-standing challenge in access to natural antifreeze materials.