Unlocking the full compositional control of hydrophilic and hydrophobic deep eutectic solvents over protein structure and stability

Abstract Deep eutectic solvents (DESs) have emerged as powerful environments to enhance enzymatic reactions, formulate therapeutic proteins, and develop protein-based biomaterials. Despite the wide range of properties that could be achievable through the compositional design of DESs, protein solubil...

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Main Authors: Adrian Sanchez-Fernandez, Jake H. Nicholson, Susana M. Meza Huaman, Claudia Almuzara Romero, Jia-Fei Poon, Sylvain Prevost, Alex P. S. Brogan
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Communications Chemistry
Online Access:https://doi.org/10.1038/s42004-025-01571-6
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Summary:Abstract Deep eutectic solvents (DESs) have emerged as powerful environments to enhance enzymatic reactions, formulate therapeutic proteins, and develop protein-based biomaterials. Despite the wide range of properties that could be achievable through the compositional design of DESs, protein solubilization only happens in a relatively narrow range of hydrophilic DESs. Here, we use surface-modification for the generalized solubilization of proteins in both hydrophilic and hydrophobic DESs. Using surface-modified myoglobin as a model, we show that both DES polarity and hydrogen bond capacity play important roles in dictating the conformational state of the protein. In the hydrophilic DES the protein displays a near-native conformation with an improvement of the thermal stability of + 28 °C compared to aqueous solutions. In contrast, hydrophobic DESs stabilize partially folded intermediates which can refold from temperatures as high as 190 °C. As such, our approach provides a platform to generalize protein incorporation into anhydrous DESs that could be exploited in biocatalysis, biomolecule stabilization, and biomaterials.
ISSN:2399-3669