Storage Stabilization of Proteins

  • Felix Franks
Part of the Biological Methods book series (BM)


Proteins in solution are subject to more or less rapid deterioration; the causes are not clearly established. Some deterioration processes were discussed in  Chapter 11. The view is held by some that proteins can never be purified to the extent that all traces of proteolytic enzymes are removed, thus making a gradual deterioration in a liquid medium unavoidable. For a proteinaceous preparation to be turned into a viable commercial product with a reasonable shelf life capable of being shipped and stored, it must be subjected to some form of treatment that will substantially retard all possible inactivation processes. Standard stabilization methods include:
  • Chemical additives [glycerol, (NH4)2SO4];

  • Undercooling (subzero temperatures, unfrozen);

  • Chemical modification/immobilization;

  • Sequence alteration/“protein engineering”;

  • Freeze/thaw, lyophilization; Water-soluble glasses.


Residual Moisture Subzero Temperature Total Solid Content Unfrozen Water Sublimation Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Wilson G. A. and Young F. E. (1975) J. Mol. Biol. 97, 123.PubMedCrossRefGoogle Scholar
  2. 2.
    Angell C. A. (1982) in Water-A Comprehensive Treatise, (Franks F., ed.), Plenum, New York, p. 1.Google Scholar
  3. 3.
    Privalov P. L. (1990) Crit. Rev., Biochem. Mol. Biol. 25, 281–306.CrossRefGoogle Scholar
  4. 4.
    Franks F. and Hatley R. H. M. (1991) Pure Appl. Chem. in press.Google Scholar
  5. 5.
    (1990) Life at Low Temperatures. The Royal Society, London.Google Scholar
  6. 6.
    Storey K. B., Baust J. G., and Storey J. M. (1981) J. Comp. Physiol. 144, 183–190.Google Scholar
  7. 7.
    Hobbs P. V. (1974) Ice Physics. Clarendon Press, OxfordGoogle Scholar
  8. 8.
    Michelmore R. W. and Franks F. (1982) Ciyobiology 19, 163–171.CrossRefGoogle Scholar
  9. 9.
    Hatley R. H. M, Franks F., and Mathias S. F. (1987) Process Biochem. 22, 169–172.Google Scholar
  10. 10.
    Franks F. (1985) Biochemistry and Biophysics at Low Temperatures. Cambridge University Press, Cambridge.Google Scholar
  11. 11.
    Warren G. J. and Wolber P. K. (1987) Cryo-Letters 8, 204–215.Google Scholar
  12. 12.
    Tomchaney A. P., Morris J. P., Kang S. H., and Duman J. G. (1982) Biochemistry 21, 716-721-730.Google Scholar
  13. 13.
    Rasmussen D. H. and MacKenzie A. P. (1972) in Water Structure at the Water-Polymer Interface (Jellinek H. J. G., ed.), Plenum, New York, p. 126.Google Scholar
  14. 14.
    Franks F. (1982) in Water, A Comprehensive Treatise, vol. 7 (Franks F., ed.), Plenum, New York, p. 215.Google Scholar
  15. 15.
    MacFarlane D. R., Kadiyala R. K., and Angell C. A. (1983) J. Chem. Phys. 79, 3921–3927.CrossRefGoogle Scholar
  16. 16.
    Luyet B. (1964) Proc. NY Acad. Sci. 125, 502–512.CrossRefGoogle Scholar
  17. 17.
    Mayer E. and Brüggeller P. (1983) J. Phys. Chem. 87, 4744–4749.CrossRefGoogle Scholar
  18. 18.
    Körber C. (1988) Quat. Rev. Biophys. 21, 229–298.CrossRefGoogle Scholar
  19. 19.
    Murase N. and Franks F. (1989) Biophys. Chem. 34, 293–300.PubMedCrossRefGoogle Scholar
  20. 20.
    Hatley R. H. M., Franks F., and Day H. (1986) Biophys. Chem. 24, 187–192.PubMedCrossRefGoogle Scholar
  21. 21.
    Fennema O. (1975), in Water Relations of Foods (Duckworth R. B., ed.), Academic, London, p. 397.Google Scholar
  22. 22.
    Brandts J. F., Fu J., and Nordin J. H. (1970) in The Frozen Cell (Wolstenholme G. E. W. and O’Connor M, eds.) J. & A. Churchill, London, p. 189.Google Scholar
  23. 23.
    Tamiya T., Okahashi N., Sakuma R., Aoyama T., Akahane T., and Matsumoto J. J. (1985) Cryobiology 22, 446–456.PubMedCrossRefGoogle Scholar
  24. 24.
    Diller K. R. and Lynch M. E. (1983) Cryo-Utters 4, 295–308.Google Scholar
  25. 25.
    Hatley R. H. M, van den Berg G, and Franks F. (1991), Cryo-Letters 12, 113–126.Google Scholar
  26. 26.
    Levine H. and Slade L. (1988) Water Sci. Rev. 3, 79–185.CrossRefGoogle Scholar
  27. 27.
    Franks F. (1990) Cryo-Letters 11, 93–110.Google Scholar
  28. 28.
    Pikal M. J. (1990) BioPharm. 3, 18–27.Google Scholar
  29. 29.
    Levine H. and Slade L. (1988) Cryo-Letters 9, 21–63.Google Scholar
  30. 30.
    Hatley R. H. M. (1992) Dev. Biol. Standardization 74, 105–122.Google Scholar
  31. 31.
    Hatley R. H. M., Franks F., and Green M. (1989) Thermochim. Ada 156, 247–257.CrossRefGoogle Scholar
  32. 32.
    Franks F. (1991) BioPharm. 4, 38–42,55.Google Scholar
  33. 33.
    Roser B. J., US Patent 4,891,319, January 2, 1990.Google Scholar
  34. 34.
    Carpenter J. F. and Crowe J. H. (1988) Cryobiology 25, 459–470.CrossRefGoogle Scholar
  35. 35.
    Franks F. and Hatley R. H. M., U.S. Patent 5,098,893, March 24, 1992.Google Scholar

Copyright information

© The Humana Press Inc 1993

Authors and Affiliations

  • Felix Franks
    • 1
  1. 1.Pafra LtdCambridgeEngland

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