Skip to main content

Interaction of the synthetic immunomodulatory dipeptide bestim with murine macrophages and thymocytes

Abstract

The tritium-labeled dipeptide bestim (γ-D-Glu-L-Trp) with a specific activity of 45 Ci/mmol was obtained by high-temperature solid-state catalytic isotope exchange. It was found that [3H]bestim binds with a high affinity to murine peritoneal macrophages (K d 2.1 ± 0.1 nM) and thymocytes (K d 3.1 ± 0.2 nM), as well as with plasma membranes isolated from these cells (K d 18.6 ± 0.2 and 16.7 ± 0.3 nM, respectively). The specific binding of [3H]bestim to macrophages and thymocytes was inhibited by the unlabeled dipeptide thymogen (L-Glu-L-Trp) (K i 0.9 ± 0.1 and 1.1 ± 0.1 nM, respectively). After treatment with trypsin, macrophages and thymocytes lost the ability to bind [3H]bestim. Bestim in the concentration range of 10−10 to 10−6 M reduced the adenylate cyclase activity in the membranes of murine macrophages and thymocytes.

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

Abbreviations

ACTH:

adrenocorticotropic hormone

PAM:

phenacylamidomethyl

γ-D-Glu:

the glutamic acid residue that forms the peptide bond through the γ-carboxyl group

References

  1. Kolobov, A. and Simbirtsev, A., Patent Application WO9933799, 1999.

  2. Simbirtsev, A., Kolobov, A., Zabolotnych, N., Pigareva, N., Konusova, V., Kotov, A., Variouchina, E., Bokovanov, V., Vinogradova, T., Vasilieva, S., and Tuthill, C., Russ. J. Immunol, 2003, vol. 8, pp. 11–22.

    CAS  PubMed  Google Scholar 

  3. Semina, O.I., Semenets, T.N., Zamulaeva, I.A., Selivanova, E.I., Malyutina, Yu.I., Saenko, A.S., and Deigin, V.I., Bull. Eksp. Biol. Med., 2006, vol. 141, pp. 250–253.

    CAS  Article  Google Scholar 

  4. Deigin, V.I., Semenets, T.N., Zamulaeva, I.A., Maliutina, Y.V., Selivanova, E.I., Saenko, A.S., and Semina, O.V., Int. Immunopharmacol., 2007, vol. 7, pp. 375–382.

    CAS  Article  PubMed  Google Scholar 

  5. Dambaeva, S.I., Kim, K.F., Mazurov, D.V., and Deigin, V.I., Zh. Mikrobiol. Epidemiol. Immunobiol., 2002, vol. 6, pp. 55–59.

    PubMed  Google Scholar 

  6. Tsvelev, Yu.V., Khavinson, V.Kh., D’yachuk, A.V., Gur’ev, A.V., and Seryi, S.V., Akush. Ginekol., 1992, no. 2, pp. 54–57.

  7. Morozova, T.I., Khudzik, L.B., and Tikhomirova, L.A., Problemy Tuberkuleza, 1994, no. 2, pp. 40–42.

  8. Yushchuk, N.D., Tseneva, G.Ya., Alenushkina, T.V., and Kulyashova, L.V., Zhurn. Mikrobiol. Epidemiol. Immunobiol., 1995, no. 3, pp. 106–108.

  9. Smith, D.L., Cai, J., Zhu, S., Wei, W., Fukmoto, J., Sharma, S., Masood, R., and Gill, P.S., Int. J. Cancer, 2003, vol. 106, pp. 528–533.

    CAS  Article  PubMed  Google Scholar 

  10. Demidov, S.V., Kostromin, A.P., Chernichenko, E.F., Kuibeda, V.V., and Borovok, M.I., Problemy Tuberkuleza, 1990, no. 10, pp. 63–65.

  11. Demidov, S.V., Kostromin, A.P., Kuibeda, V.V., Chernaya, I.V., and Borovok, M.I., Ukr. Biokhim. Zh., 1991, vol. 63, pp. 104–106.

    CAS  PubMed  Google Scholar 

  12. Boichenko, M.N. and Zhilina, I.L., Zh. Mikrobiol. Epidemiol. Immunobiol., 1983, no. 5, pp. 9–12.

  13. Zhilina, I.L., Elkina, S.I., and Boichenko, M.N., Zh. Mikrobiol. Epidemiol. Immunobiol., 1984, no. 6, pp. 98–101.

  14. Ueda, H., Yoshihara, Y., Misawa, H., Fukushima, N., Katada, T., Ui, M., Takagi, H., and Satoh, M., J. Biol. Chem., 1989, vol. 264, pp. 3732–3741.

    CAS  PubMed  Google Scholar 

  15. Zolotarev, Y.A., Dadayan, A.K., Bocharov, E.V., Borisov, Y.A., Vaskovsky, B.V., Dorokhova, E.M., and Myasoedov, N.F., Amino Acids, 2003, vol. 24, pp. 325–333.

    CAS  Article  PubMed  Google Scholar 

  16. Navolotskaya, E.V., Struktural and Functional Study of Human 2-Interferone, Interluekin-2, and Immunoglobulin G with the Use of Synthetic Peptidess, Doctoral (Biol.) Dissertation, Moscow: Institute of Immunology, 1994.

    Google Scholar 

  17. Uchitel’, I.Ya., Makrofagi v immunitete (Macrophages in Immunity), Moscow: Meditsina, 1978.

    Google Scholar 

  18. Dal Farra, C., Zsurger, N., Vincent, J.-P., and Cupo, A., Peptides, 2000, vol. 21, pp. 577–587.

    Article  Google Scholar 

  19. Lowry, O.H., Rosenbrough, N.J., Farr, O.L., and Randal, R.J., J. Biol. Chem., 1951, vol. 193, pp. 265–275.

    CAS  PubMed  Google Scholar 

  20. Chang, K.-J., Jacobs, S., and Cuatrecasas, P., Biochim. Biophys. Acta, 1975, vol. 406, pp. 294–303.

    CAS  Article  PubMed  Google Scholar 

  21. Cheng, Y.C. and Prusoff, W., Biochem. Pharmacol., 1973, vol. 22, pp. 3099–3108.

    CAS  Article  PubMed  Google Scholar 

  22. Navolotskaya, E.V., Kovalitskaya, Yu.A., Zolotarev, Yu.A., Kolobov, A.A., Kampe-Nemm, E.A., Zargarova, T.A., Malkova, N.V., Yurovskii, V.V., and Lipkin, V.M., Biokhimiya (Moscow), 2004, vol. 69, pp. 488–496.

    Google Scholar 

  23. Saltarelli, D., Fischer, S., and Gacon, G., Biochem. Biophys. Res. Commun., 1985, vol. 127, pp. 318–325.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. V. Navolotskaya.

Additional information

Original Russian Text © A.A. Kolobov, N.I. Kolodkin, Yu.A. Zolotarev, C. Tuthill, E.V. Navolotskaya, 2008, published in Bioorganicheskaya Khimiya, 2008, Vol. 34, No. 1, pp. 43–49.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kolobov, A.A., Kolodkin, N.I., Zolotarev, Y.A. et al. Interaction of the synthetic immunomodulatory dipeptide bestim with murine macrophages and thymocytes. Russ J Bioorg Chem 34, 37–42 (2008). https://doi.org/10.1134/S1068162008010044

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162008010044

Key words

  • adenylate cyclase
  • immune system
  • peptides
  • receptors