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The immunoregulatory effects of edeine analogues in mice


The edeines analogs were tested in several in vitro and in vivo assays using the mouse model, with edeine B (peptide W1) and cyclosporine A as reference compounds. The peptides displayed moderate, stimulatory effects on concanavalin A-induced (ConA-induced) splenocyte proliferation, whereas their effects on pokeweed mitogen-induced (PWM-induced) splenocyte proliferation were inhibitory. The peptides inhibited lipopolysacharide-induced (LPS-induced) tumor necrosis factor alpha production but had little effect on interleukin 6 production. In the model of the humoral immune response in vitro to sheep red blood cells, peptide 1 was distinctly stimulatory in the investigated concentrations (1-100 μg/ml), whereas peptides 3 and 4 only stimulated the number of antibody-forming cells at the highest concentration (100 μg/ml). In the model of the delayed type hypersensitivity in vivo to ovalbumin, the peptides were moderately suppressive (3 being the most active). The reference peptide W1 stimulated ConA-induced cell proliferation at 1–10 μg/ml but was inhibitory at 100 μg/ml. It also inhibited PWM-induced cell proliferation in a dose-dependent manner. This peptide had no effect on the humoral immune response in vitro or on cytokine production, but inhibited DTH reaction in vivo. The relationship between structure and activity, and a possible mode of action of the peptides, is discussed in this paper.



antibody-forming cells


complete Freund’s adjuvant

Con A:

concanavalin A




delayed type hypersensitivity


incomplete Freund’s adjuvant




optical density




pokeweed mitogen


sheep red blood cells


  1. Kuryło-Borowska, Z. Antibiotical properties of the strain Bacillus brevis Vm4. Bull. Inst. Marine Med. Gdańsk 10 (1959) 83–98.

    Google Scholar 

  2. Kuryło-Borowska, Z. Isolation and properties of pure edeine, an antibiotic of the strain Bacillus brevis Vm4. Bull. Inst. Marine Med. Gdańsk 10 (1959) 151–163.

    Google Scholar 

  3. Borowski, E., Chmara, H. and Jereczek-Morawska, E. The antibiotic edeine. VI. Paper and thin-layer chromatography of components of the edeine complex. Biochim. Biophys. Acta 130 (1966) 560–563.

    CAS  PubMed  Google Scholar 

  4. Hettinger, T.P. and Craig, L.C. Edeine. IV. Structures of the antibiotic peptides edeines A1 and B1. Biochemistry 9 (1970) 1224–1232.

    Article  CAS  PubMed  Google Scholar 

  5. Wojciechowska, H., Zgoda, W., Borowski, E., Dzięgielewski, K. and Ulikowski, S. The antibiotic edeine. XII. Isolation and structure of edeine F. J. Antibiot. 36 (1983) 793–798.

    CAS  PubMed  Google Scholar 

  6. Wojciechowska, H., Konitz, A. and Borowski, E. The antibiotic edeine. XI. Chemical structure of edeine D. Int. J. Peptide Protein Res. 26 (1985) 279–293.

    Article  CAS  Google Scholar 

  7. Chmara, H. and Borowski, E. Antibiotic edeine: VII. Biological activity of edeine A and B. Acta Microbiol. Polon. 17 (1968) 59–66.

    CAS  Google Scholar 

  8. Borysiewicz, J. Effect of various inhibitors of protein and deoxyribonucleic acid synthesis on the growth of Mycoplasmas. Appl. Microbiol. 14 (1966) 1049–1050.

    CAS  PubMed  Google Scholar 

  9. Borowski, J., Jakoniuk, P., Jabłońska, W. and Borowski, E. Effect of edeine on primary immunologic response in mice. Arch. Immun. Ther. Exp. 23 (1975) 195–199.

    CAS  Google Scholar 

  10. Kierońska, D., Różalska, B. and Zabłocki, B. Immunosuppressive properties of the antibiotic edeine. Bull. Acad. Polon. Sci. Ser. Sci. Biol. 24 (1976) 705–710.

    Google Scholar 

  11. Borowski, J., Jakoniuk, P. and Borowski, E. Edeine as an immunosuppressive agent. Drugs Exptl. Clin. Res. 3 (1977) 183–188.

    CAS  Google Scholar 

  12. Kuryło-Borowska, Z. On the mode of action of edeine. Effect of edeine on the bacterial DNA. Biochim. Biophys. Acta 87 (1964) 305–313.

    PubMed  Google Scholar 

  13. Borowski, E. and Chmara, H. The antibiotic edeine. VIII: The mode of action of edeine A and B. Acta Microbiol. Polon. 17 (1968) 241–238.

    CAS  Google Scholar 

  14. Kuryło-Borowska, Z. and Szer, W. Inhibition of bacterial DNA synthesis by edeine. Effect on Escherichia coli mutants lacking DNA polymerase I. Biochim. Biophys. Acta 287 (1972) 236–245.

    PubMed  Google Scholar 

  15. Woynarowska, B., Chmara, H. and Borowski, E. Differential mechanism of action of the antibiotic edeine on prokaryotic and eukaryotic organism points to new basis for selective toxicity. Drugs Exptl. Clin. Res. 5 (1979) 181–186.

    CAS  Google Scholar 

  16. Hierowski, M. and Kuryło-Borowska, Z. On the mode of action of edeine. I. Effect of edeine on the synthesis of polyphenylalanine in a cell-free system. Biochim. Biophys. Acta 95 (1965) 578–589.

    CAS  PubMed  Google Scholar 

  17. Obrig, T., Irvin, J., Culp, W. and Hardesty, B. Inhibition of peptide initiation on reticulocyte ribosomes by edeine. Eur. J. Biochem. 21 (1971) 31–41.

    Article  CAS  PubMed  Google Scholar 

  18. Pioletti, M., Schlunzen, F., Harms, J., Zarivach, R., Gluhmann M., Avila, H., Bashan, A., Bartels, H., Auerbach, T., Jacobi, C., Hartsch, T., Yonath, A. and Franceschi, F. Crystal structures of complexes of the small ribosomal subunit with tetracycline, edeine and IF3. EMBO J. 20 (2001) 1829–1839.

    Article  CAS  PubMed  Google Scholar 

  19. Dinos, G., Wilson, D.N., Teraoka, Y., Szaflarski, W., Fucini, P., Kalpaxis, D. and Nierhaus K.H. Dissecting the ribosomal inhibition mechanisms of edeine and pactamycin: The universally conserved residues G693 and C795 regulate P-site RNA binding. Mol. Cell 13 (2004)113–124.

    Article  CAS  PubMed  Google Scholar 

  20. Mazerski, J., Wojciechowska, H., Zgoda, W., Wojnarowska, B. and Borowski, E. Esters and amides of edeine A. J. Antibiot. 34 (1981) 28–33.

    CAS  PubMed  Google Scholar 

  21. Gumieniak, J., Andruszkiewicz, R., Czerwiński, A., Grzybowska, J. and Borowski, E. Synthesis of the decarboxy analog of edeine D. J. Antibiot. 36 (1983) 1239–1241.

    CAS  PubMed  Google Scholar 

  22. Czajgucki, Z., Andruszkiewicz, R. and Kamysz, W. Synthesis and antimicrobial activity of novel edeines A and D analogues. J. Peptide Sci. 12 (2006) 653–662.

    Article  CAS  Google Scholar 

  23. Czajgucki, Z. PhD Thesis, Gdańsk University of Technology, Gdańsk, Poland, 2006.

  24. Hansen, M.B., Nielsen, S.E. and Berg, K. Reexamination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J. Immunol. Methods 119 (1989) 203–210.

    Article  CAS  PubMed  Google Scholar 

  25. Espevik, T. and Nissen-Meyer, J. A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes. J. Immunol. Methods 95 (1986) 99–105.

    Article  CAS  PubMed  Google Scholar 

  26. Van Snick, J., Vink, A., Uyttenhove, C., Coulie, P.G., Rubira, M.R. and Simpson, R.J. Purification and NH2-terminal amino acid sequence of a T-cell derived lymphokine with growth factor activity for B-cell lynphokine with growth factor activity for B-cell hybridomas. PNAS 83 (1986) 9679–9683.

    Article  PubMed  Google Scholar 

  27. Mishell, R.I. and Dutton, R.W. Immunization of dissociated spleen cell cultures from normal mice. J. Exp. Med. 126 (1967) 423–442.

    Article  CAS  PubMed  Google Scholar 

  28. Lagrange, P.H., Mackaness, G.B. and Miller, T.E., Pardon, P. Influence of dose and route of antigen injection on the immunological induction of T cells. J. Exp. Med. 139 (1974)528–542.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Michał Zimecki.

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Czajgucki, Z., Zimecki, M. & Andruszkiewicz, R. The immunoregulatory effects of edeine analogues in mice. Cell Mol Biol Lett 12, 149–161 (2007).

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