An Ultra-Potent, Ultra-Economical, Antifreeze Polypeptide

25 February 2025, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

The coarsening of 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, were prepared using economical methodology, are thermally stable, are biodegradable, and are non-toxic to human cells. Mirror-image polypeptides resisted degradation and are suitable for applications with a longevity criterion. Their α-helical conformation played a role in antifreeze activity, but chirality did 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.

Keywords

antifreeze
IRI
cryopreservation
cryoprotectant
polypeptide
N-carboxyanhydride

Supplementary materials

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Supplementary Information
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Full experimental details, additional data, and characterization of compounds can be found in the Supporting Information (SI). Data is available on request from the authors.
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