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Low-Transition-Temperature Mixtures (LTTMs) for Dissolving Proteins and for Drug Formulation

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Abstract

Several diverse proteins are found to readily dissolve in neat low-transition-temperature mixtures (LTTMs). They undergo no irreversible denaturation in such unusual solvents, and the resistance of hen egg-white lysozyme against thermoinactivation in LTTMs is greater than in aqueous solution at extreme pHs. Separately, the water-sensitive drug aspirin is found to form concentrated transparent LTTMs, where it is some 10-fold more stable against cleavage than in water.

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References

  1. Augustin, P., & Brewster, M. E. (Eds.) (2007). Non-aqueous systems for formulation development—proteins. New York:Springer.

    Google Scholar 

  2. Torres, S., & Castro, G. R. (2004). Non-aqueous biocatalysis in homogeneous solvent systems. Food Technology and Biotechnology, 42, 271–274.

    CAS  Google Scholar 

  3. Klibanov, A. M. (2001). Improving enzymes by using them in organic solvents. Nature, 409, 241–246.

    Article  CAS  Google Scholar 

  4. Tonova, K., & Lazarova, Z. (2008). Reversed micelle solvents as tools of enzyme purification and enzyme-catalyzed conversion. Biotechnology Advances, 26, 516–532.

    Article  CAS  Google Scholar 

  5. Chin, J. T., Wheeler, S. L., & Klibanov, A. M. (1994). On protein solubility in organic solvents. Biotechnology and Bioengineering, 44, 140–145.

    Article  CAS  Google Scholar 

  6. Bihari, M., Russell, T. P., & Hoagland, D. A. (2010). Dissolution and dissolved state of cytochrome c in a neat, hydrophilic ionic liquid. Biomacromolecules, 11, 2944–2948.

    Article  CAS  Google Scholar 

  7. Francisco, M., van den Bruinhorst, A., & Kroon, M. C. (2013). Low-transition-temperature mixtures (LTTMs): a new generation of designer solvents. Angewandte Chemie, International Edition, 52, 3074–3085.

    Article  CAS  Google Scholar 

  8. Abbott, A. P., Capper, G., Davies, D. L., Rasheed, R. K., & Tambyrajah, V. (2003). Novel solvent properties of choline chloride/urea mixtures. Chemical Communications, 1, 70–71.

    Article  Google Scholar 

  9. Zhang, Q. H., Vigier, K. D. O., Royer, S., & Jérôme, F. (2012). Deep eutectic solvents: syntheses, properties and applications. Chemical Society Reviews, 41, 7108–7146.

    Article  CAS  Google Scholar 

  10. Russ, C., & König, B. (2012). Low melting mixtures in organic synthesis-an alternative to ionic liquids? Green Chemistry, 14, 2969–2982.

    Article  CAS  Google Scholar 

  11. Du, W., & Klibanov, A. M. (2011). Hydrophobic salts markedly diminish viscosity of concentrated protein solutions. Biotechnology and Bioengineering, 108, 632–636.

    Article  CAS  Google Scholar 

  12. Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Chemistry, 72, 248–254.

    CAS  Google Scholar 

  13. Baker, S. N., McCleskey, T. M., Pandey, S., & Baker, G. A. (2004). Fluorescence studies of protein thermostability in ionic liquids. Chemical Communications, 8, 940–941.

    Article  Google Scholar 

  14. Lau, R. M., Sorgedrager, M. J., Carrea, G., van Rantwijk, F., Secundo, F., & Sheldon, R. A. (2004). Dissolution of Candida antarctica lipase B in ionic liquids: effects on structure and activity. Green Chemistry, 6, 483–487.

    Article  Google Scholar 

  15. Avanti, C., Saluja, V., van Streun, E. L. P., Frijlink, H. W., & Hinrichs, W. L. J. (2014). Stability of lysozyme in aqueous extremolyte solutions during heat shock and accelerated thermal conditions. PloS One, 9, e86244.

    Article  Google Scholar 

  16. Xu, K., Griebenow, K., & Klibanov, A. M. (1997). Correlation between catalytic activity and secondary structure of subtilisin dissolved in organic solvents. Biotechnology and Bioengineering, 56, 485–491.

    Article  CAS  Google Scholar 

  17. Reichardt, C., & Welton, T. (Eds.) (2011). Solvents and solvent effects in organic chemistry (4th ed., ). Weinheim:Wiley-VCH.

    Google Scholar 

  18. Ahern, T. J., & Klibanov, A. M. (1988). Analysis of processes causing thermal inactivation of enzymes. Methods of Biochemical Analysis, 33, 91–127.

    Article  CAS  Google Scholar 

  19. Byrne, N., Wang, L. M., Belieres, J. P., & Angell, C. A. (2007). Reversible folding-unfolding, aggregation protection, and multi-year stabilization, in high concentration protein solutions, using ionic liquids. Chemical Communications, 26, 2714–2716.

    Article  Google Scholar 

  20. Edwards, L. J. (1950). The hydrolysis of aspirin. A determination of the thermodynamic dissociation constant and a study of the reaction kinetics by ultra-violet spectrophotometry. Transactions of the Faraday Society, 46, 723–735.

    CAS  Google Scholar 

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Acknowledgments

Erzheng Su thanks the China Scholarship Council and Nanjing Forestry University for an Overseas Visiting Scholarship.

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Authors and Affiliations

  1. Departments of Chemistry and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Erzheng Su & Alexander M. Klibanov

  2. Enzyme and Fermentation Technology Laboratory, College of Light Industry Science and Engineering, Nanjing Forestry University, Nanjing, 210037, China

    Erzheng Su

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  1. Erzheng Su
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  2. Alexander M. Klibanov
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Correspondence to Alexander M. Klibanov.

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Su, E., Klibanov, A.M. Low-Transition-Temperature Mixtures (LTTMs) for Dissolving Proteins and for Drug Formulation. Appl Biochem Biotechnol 177, 753–758 (2015). https://doi.org/10.1007/s12010-015-1777-x

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  • DOI: https://doi.org/10.1007/s12010-015-1777-x

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