Biochemistry (Moscow)

, Volume 73, Issue 4, pp 432–441 | Cite as

Interaction of chitosans and their N-acylated derivatives with lipopolysaccharide of gram-negative bacteria

  • G. A. NaberezhnykhEmail author
  • V. I. Gorbach
  • G. N. Likhatskaya
  • V. N. Davidova
  • T. F. Solov’eva


The interactions of lipopolysaccharide (LPS) with the natural polycation chitosan and its derivatives—high molecular weight chitosans (80 kD) with different degree of acetylation, low molecular weight chitosan (15 kD), acylated oligochitosan (5.5 kD) and chitooligosaccharides (biose, triose, and tetraose)—were studied using ligand-enzyme solid-phase assay. The LPS-binding activity of chitosans (80 kD) decreased with increase in acetylation degree. Affinity of LPS interaction with chitosans increased after introduction of a fatty acid residue at the reducing end of chitosan. Activity of N-monoacylated chitooligosaccharides decreased in the order: oligochitosan → tetra-→ tri-→ disaccharides. The three-dimensional structures of complexes of R-LPS and chitosans with different degree of acetylation, chitooligosaccharides, and their N-monoacylated derivatives were generated by molecular modeling. The number of bonds stabilizing the complexes and the energy of LPS binding with chitosans decreased with increase in acetate group content in chitosans and resulted in changing of binding sites. It was shown that binding sites of chitooligosaccharides on R-LPS overlapped and chitooligosaccharide binding energies increased with increase in number of monosaccharide residues in chitosan molecules. The input of the hydrophobic fragment in complex formation energy is most prominent for complexes in water phase and is due to the hydrophobic interaction of chitooligosaccharide acyl fragment with fatty acid residues of LPS.

Key words

lipopolysaccharide chitosan binding computer simulation molecular docking 



biotinylated low molecular weight chitosan






high molecular weight chitosan


ligand-enzyme solid-phase assay


low molecular weight chitosan




Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Raetz, C. R. H., and Whitfield, C. (2002) Annu. Rev. Biochem., 71, 635–700.PubMedCrossRefGoogle Scholar
  2. 2.
    Ferguson, A. D., Welte, W., Hofmann, E., Linder, B., Holst, O., Coulton, J. W., and Diederichs, K. (2000) Structure, 8, 585–592.PubMedCrossRefGoogle Scholar
  3. 3.
    Brandenburg, K., and Wiese, A. (2004) Curr. Top. Med. Chem., 4, 1127–1146.PubMedCrossRefGoogle Scholar
  4. 4.
    Andra, J., Gutsmann, Th., Garidel, P., and Brandenburg, K. (2006) J. Endotoxin Res., 12, 261–277.PubMedGoogle Scholar
  5. 5.
    Bowdish, D. M. E., and Hancock, R. W. E. (2005) J. Endotoxin Res., 11, 230–236.PubMedGoogle Scholar
  6. 6.
    David, S. A. (2001) J. Mol. Recognit., 14, 370–387.PubMedCrossRefGoogle Scholar
  7. 7.
    Zorko, M., Majerle, A., Sarlah, D., Keber, M. M., Mohar, B., and Jerala, R. (2005) Antimicr. Agents Chemother., 49, 2307–2313.CrossRefGoogle Scholar
  8. 8.
    David, S. A., Silverstein, R., Amura, C. R., Kielain, T., and Morrison, D. C. (1999) Antimicr. Agents Chemother., 43, 912–916.Google Scholar
  9. 9.
    Millera, E. V. K., Kumarb, S., Wooda, S. J., Cromera, J. R., Dattab, A., and David, S. A. (2005) J. Med. Chem., 48, 2589–2599.CrossRefGoogle Scholar
  10. 10.
    Guo, J. X., Wood, S. J., David, S. A., and Lushington, G. H. (2006) Bioorg. Med. Chem. Lett., 16, 714–717.PubMedCrossRefGoogle Scholar
  11. 11.
    Davidova, V. N., Naberezhnykh, G. A., Yermak, I. M., Gorbach, V. I., and Solov’eva, T. F. (2006) Biochemistry (Moscow), 71, 332–339.CrossRefGoogle Scholar
  12. 12.
    Davydova, V. N., Ermak, I. M., Gorbach, V. I., Drozdov, A. L., and Solov’eva, T. F. (2000) Biophysics (Moscow), 45, 624–630.Google Scholar
  13. 13.
    Hasegawa, M. I., Isogai, A., and Onabe, F. (1994) Carbohydr. Res., 262, 161–166.CrossRefGoogle Scholar
  14. 14.
    Dische, Z. (1962) in Methods in Carbohydrate Chemistry (Whistler, R. L., and Wolfrom, M. L., eds.) Vol. 1, Academic Press Inc., New York, p. 477.Google Scholar
  15. 15.
    Gorbach, V. I., Krasikova, I. N., Lukyanov, P. A., Loenko, Y. N., Soloveva, T. F., Ovodov, Y. S., Deev, V. V., and Pimenov, A. A. (1994) Carbohydr. Res., 260, 73–82.PubMedCrossRefGoogle Scholar
  16. 16.
    Mokrasch, L. C. (1967) Analyt. Biochem., 18, 64–71.CrossRefGoogle Scholar
  17. 17.
    Der Balin, G. P., Gomez, B., Masino, R. S., and Parce, J. W. (1990) J. Immunol. Meth., 126, 281–285.CrossRefGoogle Scholar
  18. 18.
    Ferguson, A. D., Hofmann, E., Coulton, J. W., Diederichs, K., and Welte, W. (1998) Science, 282, 2215–2220.PubMedCrossRefGoogle Scholar
  19. 19.
    Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Shindyalov, I. N., and Bourne, P. E. (2000) Nucleic Acids Res., 28, 235–242.PubMedCrossRefGoogle Scholar
  20. 20.
    Jiang, G.-B., and Quan, D. (2006) Carbohydr. Polym., 66, 514–520.CrossRefGoogle Scholar
  21. 21.
    Gorbach, V. I., and Shentsova, E. B. (1999) Khim.-Farm. Zh., 11, 6–8.Google Scholar
  22. 22.
    Davydova, V. N., Yermak, I. M., Gorbach, V. I., Krasikova, I. N., and Solov’eva, T. F. (2000) Biochemistry (Moscow), 65, 1082–1090.Google Scholar
  23. 23.
    Varfolomeev, S. D., and Gurevich, K. G. (1999) Biokinetics [in Russian], FairPress, Moscow, pp. 395–396.Google Scholar
  24. 24.
    Anthonsen, M. W., Varum, K. V., and Smidsrod, O. (1993) Carbohydr. Polym., 22, 193–201.CrossRefGoogle Scholar
  25. 25.
    Kayitmazer, A. B., Shaw, D., and Dubin, P. L. (2005) Macromolecules, 38, 5198–5204.CrossRefGoogle Scholar
  26. 26.
    Kayitmazer, A. B., Seyrec, E., Dubin, P. L., and Staggemeier, B. A. (2003) J. Phys. Chem. B, 107, 8158–8165.CrossRefGoogle Scholar
  27. 27.
    Yanagisawa, M., Kato, Y., Yoshida, Y., and Isogai, A. (2006) Carbohydr. Polym., 66, 192–198.CrossRefGoogle Scholar

Copyright information

© MAIK Nauka 2008

Authors and Affiliations

  • G. A. Naberezhnykh
    • 1
    Email author
  • V. I. Gorbach
    • 1
  • G. N. Likhatskaya
    • 1
  • V. N. Davidova
    • 1
  • T. F. Solov’eva
    • 1
  1. 1.Pacific Institute of Bioorganic ChemistryFar East Division of the Russian Academy of SciencesVladivostokRussia

Personalised recommendations