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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author Adrian Sanchez-Fernandez
Jake H. Nicholson
Susana M. Meza Huaman
Claudia Almuzara Romero
Jia-Fei Poon
Sylvain Prevost
Alex P. S. Brogan
author_facet Adrian Sanchez-Fernandez
Jake H. Nicholson
Susana M. Meza Huaman
Claudia Almuzara Romero
Jia-Fei Poon
Sylvain Prevost
Alex P. S. Brogan
author_sort Adrian Sanchez-Fernandez
collection DOAJ
description 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.
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publisher Nature Portfolio
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series Communications Chemistry
spelling doaj-art-59eab83d98a74c78a2af9d94ab6698212025-08-20T02:05:46ZengNature PortfolioCommunications Chemistry2399-36692025-06-01811710.1038/s42004-025-01571-6Unlocking the full compositional control of hydrophilic and hydrophobic deep eutectic solvents over protein structure and stabilityAdrian Sanchez-Fernandez0Jake H. Nicholson1Susana M. Meza Huaman2Claudia Almuzara Romero3Jia-Fei Poon4Sylvain Prevost5Alex P. S. Brogan6Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Departamento de Enxeñaría Química Universidade de Santiago de CompostelaDepartment of Chemistry, King’s College LondonDepartment of Chemistry, King’s College LondonDepartment of Chemistry, King’s College LondonEuropean Spallation SourceInstitut Laue-Langevin – The European Neutron Source, DS/LSSDepartment of Chemistry, King’s College LondonAbstract 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.https://doi.org/10.1038/s42004-025-01571-6
spellingShingle Adrian Sanchez-Fernandez
Jake H. Nicholson
Susana M. Meza Huaman
Claudia Almuzara Romero
Jia-Fei Poon
Sylvain Prevost
Alex P. S. Brogan
Unlocking the full compositional control of hydrophilic and hydrophobic deep eutectic solvents over protein structure and stability
Communications Chemistry
title Unlocking the full compositional control of hydrophilic and hydrophobic deep eutectic solvents over protein structure and stability
title_full Unlocking the full compositional control of hydrophilic and hydrophobic deep eutectic solvents over protein structure and stability
title_fullStr Unlocking the full compositional control of hydrophilic and hydrophobic deep eutectic solvents over protein structure and stability
title_full_unstemmed Unlocking the full compositional control of hydrophilic and hydrophobic deep eutectic solvents over protein structure and stability
title_short Unlocking the full compositional control of hydrophilic and hydrophobic deep eutectic solvents over protein structure and stability
title_sort unlocking the full compositional control of hydrophilic and hydrophobic deep eutectic solvents over protein structure and stability
url https://doi.org/10.1038/s42004-025-01571-6
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