Skip to main content

Nanocomplexes of recombinant proteins and polysialic acid: Preparation, characteristics, and biological activity

Abstract

A preparation of nanocomplexes containing recombinant proteins (interferons α2b and β1b, insulin, and human granulocyte colony stimulating factor) and natural polysialic acid (PSA) has been described. The incorporation of protein into the complex changes its electrophoretic mobility. Atomic force microscopy reveals the average size of 23-kD insulin complexes with PSA of 10–20 nm and demonstrates that more than 60% of glycopolymer molecules carry a single protein molecule. Experiments with cultured cells show that cytokines bound to polysialic acid retain their ability to regulate cell proliferation. Insulin bound to PSA has a prolonged hypoglycemic effect in vivo.

This is a preview of subscription content, access via your institution.

Abbreviations

G-CSF:

human granulocyte colonysfimulating factor

IFNα2b:

interferon α2β

IFNβ1b:

interferon β1b

HOPG:

high-oriented pyrolyfic graphite

PSA:

polysialie acid

PEG:

polyethylene glycol

References

  1. Veronese, F.M. and Pasut, G., Drug Discovery Today, 2005, vol. 10, pp. 1451–1458.

    PubMed  Article  CAS  Google Scholar 

  2. Gregoriadis, G., McCormack, B., Wang, Z., and Lifely, R., FEBS Lett., 1993, vol. 315, pp. 271–276.

    PubMed  Article  CAS  Google Scholar 

  3. Gascon, E., Vutskits, L., and Kiss, J.Z., Curr. Org. Chem., 2007, vol. 11, pp. 627–635.

    Article  CAS  Google Scholar 

  4. Rohr, T.E. and Troy, F.A., J. Biol. Chem., 1980, vol. 250, pp. 2332–2342.

    Google Scholar 

  5. Jain, S., Hreczuk-Hirsta, D.H., McCormack, B., Mital, M., Epenetos, A., Laing, P., and Gregoriadis, G., Biochim. Biophys. Acta, 2003, vol. 1622, pp. 42–49.

    PubMed  CAS  Google Scholar 

  6. Fernandes, A.I. and Gregoriadis, G., Biochim. Biophys. Acta, 1997, vol. 1341, pp. 26–34.

    PubMed  CAS  Google Scholar 

  7. Bezuglov, V.V., Gretskaya, N.M., Bobrov, M.Yu., Akimov, M.G., Fomina-Ageeva, E.V., Zinchenko, G.N., Bairamashvili, D.I., and Miroshnikov, A.I., Bioorg.. Khim., 2009, vol. 35 [Russ. J. Bioorg. Chem. (Engl. Transl.), vol. 35] (in press).

  8. Möhlenhoff, M., Eckhardt, M., and Gerardy-Schahn, R., Curr. Opin. Struct. Biol., 1998, vol. 8, pp. 558–564.

    Article  Google Scholar 

  9. Klinov, D., Dwir, B., Kapon, E., Borovok, N., Molotsky, T., and Kotlyar, A., Nanotecnology, 2007, vol. 18, pp. 225102–225108.

    Article  Google Scholar 

  10. Adamcik, J., Klinov, D.V., Witz, G., Sekatskii, S.K., and Dietler, G., FEBS Lett., 2006, vol. 580, pp. 5671–5675.

    PubMed  Article  CAS  Google Scholar 

  11. Ovodova, R.G., Popov, S.V., Bushneva, O.A., Golovchenko, V.V., Chizhov, A.O., Klinov, D.V., and Ovodov, Yu.S., Biochemistry (Moscow), 2006, vol. 71, pp. 538–542.

    Article  CAS  Google Scholar 

  12. Klinov, D. and Magonov, S., Appl. Phys. Lett., 2004, vol. 84, pp. 2697–2699.

    Article  CAS  Google Scholar 

  13. Ramon, J., Saez, V., Baez, R., Aldana, R., and Hardy, E., Pharm. Res., 2005, vol. 22, pp. 1374–1386.

    PubMed  Article  CAS  Google Scholar 

  14. Yamaguchi, T., Kogi, M., Yamamoto, Y., and Hayakawa, T., Biol. Pharm. Bull., 1997, no. 9, pp. 943–947.

  15. Stoscheck, C.M., Methods Enzymol., 1990, vol. 182, pp. 50–69.

    PubMed  Article  CAS  Google Scholar 

  16. Svennerholm, L., Methods Enzymol., 1963, vol. 6, pp. 459–462.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. V. Bezuglov.

Additional information

Original Russian Text © V.V. Bezuglov, N.M. Gretskaya, D.V. Klinov, M.Yu. Bobrov, E.D. Shibanova, M.G. Akimov, E.V. Fomina-Ageeva, G.N. Zinchenko, D.I. Bairamashvili, A.I. Miroshnikov, 2009, published in Bioorganicheskaya Khimiya, 2009, Vol. 35, No. 3, pp. 350–356.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bezuglov, V.V., Gretskaya, N.M., Klinov, D.V. et al. Nanocomplexes of recombinant proteins and polysialic acid: Preparation, characteristics, and biological activity. Russ J Bioorg Chem 35, 320–325 (2009). https://doi.org/10.1134/S1068162009030066

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162009030066

Key words

  • recombinant human insulin
  • interferons
  • granulocyte colony stimulating factor
  • polysialic acid
  • nanocomplexes