This artwork by Jhoan Sebastian Aguilar, an undergraduate student doing research in the Pielak Group, made the issue's cover.

Protecting Dessicated Enzymes

Protein‐based drugs called biologics are among the most effective therapeutic treatments available. However, these drugs are unstable and require refrigerated storage, which makes them expensive. Manufacturers increase the shelf‐life of biologics by adding excipients, molecules that protect active ingredients, but most still require refrigeration. Some potential biologics may never reach the market because of this instability, and discovering better excipients would make these products not only more affordable and accessible, but also available for poor and remote populations without access to refrigeration.

In search of new, more robust excipients, gradate student Samantha Piszkiewicz along with her colleagues in the Pielak Group, as published in Protein Science, turned to the tardigrade, a microscopic animal that synthesizes cytosolic abundant heat soluble, CAHS, proteins to protect its cellular components during desiccation.

Venn Diagram

Venn diagram of additives tested as potential protectants and their categorization. Most additives fall into multiple categories. *Glycine is an amino acid and osmolyte.

The group members learned that CAHS proteins protect the test enzymes lactate dehydrogenase and lipoprotein lipase against desiccation‐, freezing‐, and lyophilization‐induced deactivation. Their data also show that a variety of globular and disordered protein controls, with no known link to desiccation tolerance, protect their test enzymes. Protection of lactate dehydrogenase correlates, albeit imperfectly, with the charge density of the protein additive, suggesting an approach to tune protection by modifying charge.

These results support the potential use of CAHS proteins as stabilizing excipients in formulations and suggest that other proteins may have similar potential, opening up potential as an excipient for biologics and for formulating industrially useful enzymes.