An Ultrapotent, Ultraeconomical, Antifreeze Polypeptide

Abstract The growth of large ice crystals during freeze and thaw events is a challenge in diverse settings from transportation and agriculture to foods and biomedicine. Design, synthesis, and evaluation of antifreeze polypeptides that inhibit ice crystal growth at µg concentrations are reported herein. The polypeptides, composed of Ala and Glu, are prepared using economical methodology, are stable after thermal events, are biodegradable, and are nontoxic to human cells. Mirror‐image polypeptides have resisted degradation and are suitable for applications with a longevity criterion. Their α‐helical conformation plays a role in antifreeze activity, but chirality does not. In proof‐of‐concept experiments, the antifreeze polypeptides could prevent damage to model protein therapeutics during repeated freeze–thaw cycles and could be applied to prevent large ice crystals in a frozen food product. These simple, economical Ala/Glu polypeptides are promising materials for diverse antifreeze applications, particularly in biological settings.