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Thermal and conformational stability of insulin in the presence of imidazolium-based ionic liquids

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Abstract

Stabilization of the monomeric form of insulin (In) under condition of low pH has been a recent challenge. This research aims to reveal the effect of a series of 1-butyl-3-methylimidazolium-based ionic liquids (ILs) on the stability of In dissolved in highly acidic solution (pH 2.0). Differential scanning calorimetry was applied to assess the thermal stability of In in the presence of these ILs. In addition, we monitored the IL-induced changes in the In secondary structure using Fourier transformed infrared spectroscopy. The peak of In thermal denaturation was shifted to higher temperatures in the presence of the tested acetate, trifluoroacetate and dicyanamide salts. At the same time, chloride and thiocyanate ILs had no effect on the thermal stability of the insulin, while the tricyanomethanide salt slightly destabilized the protein. The change in the In conformation affected not only the position but also the sharpness and the shape of the transition peak. As a whole, those ILs which were able to preserve or enhance helical structure of In produced stabilizing effect and those which stimulated the formation of unordered and random-coiled structures deteriorated its thermal stability. No aggregation of In in the presence of the imidazolium-based ILs was observed under the tested acidic media.

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References

  1. Huus K, Havelund S, Olsen H, van de Weert M, Frokjaer S. Thermal dissociation and unfolding of insulin. Biochemistry. 2005;44:11171–7.

    Article  CAS  Google Scholar 

  2. Brange J. Galenics of insulin: the physico-chemical and pharmaceutical aspects of insulin and insulin preparations. Berlin/Heidelberg: Springer; 1987.

    Book  Google Scholar 

  3. WHO media centre. Diabetes. Fact sheet. World health organization. 2015. http://www.who.int/mediacentre/factsheets/fs312/en/. Updated Jan 2015.

  4. Gualandi-Signorini AM, Giorgi G. Insulin formulations—a review. Eur Rev Med Pharmacol. 2001;5:73–83.

    CAS  Google Scholar 

  5. Brange J, Langkjær L. Insulin formulation and delivery. In: Sanders L, Hendren W, editors. Protein delivery: physical systems. New York: Plenum Press; 1997. p. 343–410.

    Google Scholar 

  6. Al-Hallak K, Sarfraz M, Azarmil S, Roa W, Finlay W, Löbenberg R. Pulmonary delivery of inhalable nanoparticles: dry powder inhalers. Ther Deliv. 2011;2:101313–24.

    Article  Google Scholar 

  7. Arbit E, Kidron M. Oral insulin: the rationale for this approach and current developments. J Diabetes Sci Technol. 2009;3:562–7.

    Article  Google Scholar 

  8. Sluzky V, Tamada J, Klibanov A, Langer R. Kinetics of insulin aggregation in aqueous solutions upon agitation in the presence of hydrophobic surfaces. Proc Natl Acad Sci USA. 1991;88:9377–81.

    Article  CAS  Google Scholar 

  9. Whittingham J, Scott D, Chance K, Wilson A, Finch J, Brange J, Dodson G. Insulin at pH 2: structural analysis of the conditions promoting insulin fibre formation. J Mol Biol. 2002;318:479–90.

    Article  CAS  Google Scholar 

  10. Mangialardo S, Gontrani L, Leonelli F, Caminiti R, Postorino P. Role of ionic liquids in protein refolding: native/fibrillar versus treated lysozyme. RSC Adv. 2012;2:12329–36.

    Article  CAS  Google Scholar 

  11. Byrne N, Angell C. Protein unfolding, and the “tuning in” of reversible intermediate states, in protic ionic liquid media. J Mol Biol. 2008;378:707–14.

    Article  CAS  Google Scholar 

  12. Böhm M, Tietze A, Heimer P, Chen M, Imhof D. Ionic liquids as reaction media for oxidative folding and native chemical ligation of cysteine-containing peptides. J Mol Liq. 2014;192:67–70.

    Article  Google Scholar 

  13. Yang Z. Hofmeister effects: an explanation for the impact of ionic liquids on biocatalysis. J Biotechnol. 2009;144:12–22.

    Article  CAS  Google Scholar 

  14. Zhao H, Olubajo O, Song Z, Sims A, Person T, Lawal R, LaDena H. Effect of kosmotropicity of ionic liquids on the enzyme stability in aqueous solutions. Bioorg Chem. 2006;34:15–25.

    Article  CAS  Google Scholar 

  15. Weingärthner H, Cabrele C, Herrmann C. How ionic liquids can help to stabilize native proteins. Phys Chem Chem Phys. 2012;14:415–26.

    Article  Google Scholar 

  16. Kumar A, Venkatesu P. The stability of insulin in the presence of short alkyl chain imidazolium-based ionic liquids. RSC Adv. 2014;4:4487–99.

    Article  CAS  Google Scholar 

  17. Kumar A, Venkatesu P. Prevention of insulin self-aggregation by protic ionic liquid. RSC Adv. 2013;3:362–7.

    Article  CAS  Google Scholar 

  18. Mahkam M, Hosseinzadeh F, Galehassadi M. Preparation of ionic liquid functionalized silica nanoparticles for oral drug delivery. J Biomat Nanobiotechnol. 2012;3:391–5.

    Article  CAS  Google Scholar 

  19. Natalello A, Ami D, Doglia SM. Fourier transform infrared spectroscopy of intrinsically disordered proteins: measurement procedures and data analyses. In: Uversky V, Dunker AK, editors. Springer Science + Business Media, Methods Mol Biol. 2012; 895:229–44.

  20. Barth A. Infrared spectroscopy of proteins. Biochim Biophys Acta. 2007;1767:1073–101.

    Article  CAS  Google Scholar 

  21. Batista M, Kurnia K, Pinho SP, Gomes J, Coutinho JAP. Computational and experimental study of the behavior of cyano-based ionic liquids in aqueous solution. J Phys Chem B. 2015;119:1567–78.

    Article  CAS  Google Scholar 

  22. Cooper A. Heat capacity effects in protein folding and ligand binding: a re-evaluation of the role of water in biomolecular thermodynamics. Biophys Chem. 2005;115:89–97.

    Article  CAS  Google Scholar 

  23. Prabhu NV, Sharp KA. Heat capacity in proteins. Annu Rev Phys Chem. 2005;56:521–48.

    Article  CAS  Google Scholar 

  24. Connelly P, Thomson J. Heat capacity changes and hydrophobic interactions in the binding of FK506 and rapamycin to the FK506 binding protein. Proc Natl Acad Sci USA. 1992;89:4781–5.

    Article  CAS  Google Scholar 

  25. Wei J, Lin Y-Z, Zhou J-M, Tsou C-L. FTIR studies of secondary structures of bovine insulin and its derivatives. Biochim Biophys Acta. 1991;1080:29–33.

    Article  CAS  Google Scholar 

  26. Fort A, Spray D. Trifluoroethanol reveals helical propensity at analogous positions in cytoplasmic domains of three connexins. Biopolymers. 2009;92:173–82.

    Article  CAS  Google Scholar 

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Correspondence to Maya Guncheva.

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Todinova, S., Guncheva, M. & Yancheva, D. Thermal and conformational stability of insulin in the presence of imidazolium-based ionic liquids. J Therm Anal Calorim 123, 2591–2598 (2016). https://doi.org/10.1007/s10973-016-5287-z

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  • DOI: https://doi.org/10.1007/s10973-016-5287-z

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