Advertisement

Molecular and Cellular Biochemistry

, Volume 41, Issue 1, pp 3–12 | Cite as

Tuftsin, a natural activator of phagocytic functions including tumoricidal activity

  • Victor A. Najjar
  • Danuta Konopinska
  • Manas K. Chaudhuri
  • Donald E. Schmidt
  • Lisa Linehan
Article

Summary

Some of the properties of the tetrapeptide tuftsin, Thr-Lys-Pro-Arg, are discussed. We describe three phases of tuftsin activation of the macrophage. Tuftsinyltuftsin, the octapeptide Thr-Lys-Pro-Arg-Thr-LysPro-Arg, was synthesized with a view of minimizing the formation of Lys-Pro-Arg, from tuftsin by tissue aminopeptidases. The tripeptide is a tuftsin inhibitor. The octapeptide proved to be quite effective in prolonging the life of syngeneic mice injected with L1210 leukemia cells. Its effect in our laboratory, was considerably better than we could obtain with tuftsin. A simple method for purifying tuftsin by high performance liquid chromatography is described using 0.75% trifluoroacetic acid in water.

The tuftsin sequence Thr-Lys-Pro-Arg is present in P 12 protein of Rausher murine leukemia virus. A close analog Thr-Arg-Pro-Lys appears in yet another virus protein the haemagglutinin of influenza virus. A second close analog Thr-Arg-Pro-Arg forms the penultimate carboxyterminal of a pancreatic polypeptide found in human and several animals.

Keywords

Leukemia Influenza Polypeptide High Performance Liquid Chromatography Influenza Virus 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Najjar, V. A. & Nishioka, K., 1970. Nature, 228: 672–673.Google Scholar
  2. 2.
    Najjar, V. A., 1974. Advances in Enzymology, Ed. A. Meister, Vol. 41, John Wiley & Sons, Inc., New York, pp. 129–278.Google Scholar
  3. 3.
    Najjar, V. A., 1980. Macrophages and Lymphocytes, Part A, Eds. M. R. Escobar & H. Friedman, Plenum Press, New York, pp. 131–147.Google Scholar
  4. 4.
    Nishioka, K., Constantopoulos, A., Satoh, P. S., Mitchell, W. M. & Najjar, V. A., 1973. Biochim. Biophys. Acta 310: 217–229.Google Scholar
  5. 5.
    Nishioka, K., Satoh, P. S., Constantopoulos, A. & Najjar, V. A., 1973. Biochim. Biophys. Acta 310: 230–237.Google Scholar
  6. 6.
    Fidalgo, B. V. & Najjar, V. A., 1967. Biochemistry, 6: 3386–3392.Google Scholar
  7. 7.
    Fidalgo, B. V. & Najjar, V. A., 1967. Proc. Natl. Acad. Sci. U.S.A. 57: 957–964.Google Scholar
  8. 8.
    Najjar, V. A., Fidalgo, B. V. & Stitt, E., 1968. Biochemistry, 7:2376–2379.Google Scholar
  9. 9.
    Najjar, V. A. & Constantopoulos, A., 1972. J. Reticuloendothel. Soc. 12: 197–215.Google Scholar
  10. 10.
    Najjar, V. A., 1975. J. Pediat. 87: 1121–1124.Google Scholar
  11. 11.
    Najjar, V. A., 1978. Exp. Cell Biol. 46: 114–126.Google Scholar
  12. 12.
    Inada, K., Nemoto, N., Nishijima, A., Wada, S., Hirata, M. & Yoshida, M., 1980. Phagocytosis: Its Physiology and Pathology, Eds. Y. Kokobun & N. Kobayashi, Vol. 1, University Park Press, Baltimore, p. 157.Google Scholar
  13. 13.
    Fridkin, M., Stabinsky, Y., Zakuth, V. & Spirer, Z., 1977. Biochim. Biophys. Acta 496: 203–211.Google Scholar
  14. 14.
    Spirer, Z., Zakuth, V., Bogair, N. & Fridkin, M., 1977. Eur. J. Immunol. 7: 69–74.Google Scholar
  15. 15.
    Najjar, V. A. & Schmidt, J. J., 1980. Lymphokine Reports, Ed. E. Pick, Vol. 1, Academic Press Inc., New York, pp. 157–159.Google Scholar
  16. 16.
    Kabat, E. A., Wu, T. T. & Bilofsky, H., 1979. U.S. Dept. of Health, Education and Welfare, Public Health Service, National Institutes of Health #80-2008.Google Scholar
  17. 17.
    Babior, B. M., 1978. N. Eng. J. Med. 298: 659–668.Google Scholar
  18. 18.
    Sbarra, A. J., Selvaraj, R. J., Paul, B. B., Poskitt, P. K. F., Zgliezynski, J. M., Mitchell, G. W., Jr. & Louis, F., 1976. Int. Rev. Exp. Pathol. 162: 249–271.Google Scholar
  19. 19.
    Spirer, Z., Zakuth, V., Golander, A., Bogair, N. & Fridkin, M., 1975. J. Clin. Invest. 55: 198–200.Google Scholar
  20. 20.
    Martinez, J., Winternitz, F. & Vindel, J., 1977. Eur. J. Med. Chem.-Chimica Therapeutica, 12: 511–516.Google Scholar
  21. 21.
    Tzehoval, E., Segal, S., Stabinsky, Y., Fridkin, M., Spirer, Z. & Feldman, M., 1978. Proc. Natl. Acad. Sci. U.S.A. 75: 3400–3404.Google Scholar
  22. 22.
    Florentin, I., Bruley-Rosset, M., Imbach, J. L., Winternitz, F. & Mathé, G., 1978. Cancer Immunol. Immunother. 5: 211–216.Google Scholar
  23. 23.
    Nishicka, K., 1979. Br. J. Cancer, 39: 342–345.Google Scholar
  24. 24.
    McBride, J. K. & Stuart, A., 1977. The Macrophage and Cancer, Symposium of the European Reticuloendothelial Society, Ed. K. James, W. McBride & A. Stuart, University of Edinburgh, Edinburgh.Google Scholar
  25. 25.
    Klebanoff, S. J. & Clark, R. A., 1978. The Neutrophils: Functions and Clinical Disorders, Ed. S. J. Klebanoff & R. A. Clark, North-Holland Publishing Co., New York.Google Scholar
  26. 26.
    Catane, R., Schlanger, S., Gottlieb, P., Halpern, J., Treves, A. J., Fuks, Z. & Fridkin, M., 1981. Abstract.Google Scholar
  27. 27.
    Najjar, V. A., Chaudhuri, M. K., Konopinska, D., Beck, B. D., Layne, P. P. & Linehan, L., 1980. Augmenting Agents of Cancer Therapy, Ed. E. M. Hersh, M. A. Chirigos & M. Mastrangelo, Raven Press, New York. p. 459.Google Scholar
  28. 28.
    Stabinsky, Y., Fridkin, M., Zakuth, V. & Spirer, Z., 1978. Int. J. Peptide Protein Res. 12: 130–138.Google Scholar
  29. 29.
    Najjar, V. A., 1963. Physiol. Rev. 43: 243–262.Google Scholar
  30. 30.
    Baldwin, D., Jr., Terris, S. & Steiner, D. F., 1980. Journal of Biological Chemistry, 255: 4028–4034.Google Scholar
  31. 31.
    Najjar, V. A., 1951. Fed. Proc. (1951): 10: 227–228.Google Scholar
  32. 32.
    Zamecnik, P., Lipmann, F., 1947. J. Exp. Med. 85: 395–403.Google Scholar
  33. 33.
    Thomaidis, T. S., Fidalgo, B. V., Harshman, S. & Najjar, V. A., 1967. Biochemistry, 6: 3369–3377.Google Scholar
  34. 34.
    Oroszlan, S., Henderson, L. E., Stephenson, J. R., Copeland, T. D., Long, C. W., Ihle, J. N. & Gilden, R. V., 1978. Proc. Natl. Acad. Sci. U.S.A. 75: 1404–1408.Google Scholar
  35. 35.
    Luftig, R. B., Yoshinaka, Y. & Oroszlan, S., 1977. J. Cell Biol. 25: 399a.Google Scholar
  36. 36.
    Suk, W. A. & Long, C. W., 1979. Am. Soc. Microbiol. 257: 105.Google Scholar
  37. 37.
    Gethings, M. J., Bye, J., Skehel, J. & Waterfield, M., 1980. Nature, 287: 301–306.Google Scholar
  38. 38.
    Blundell, T. L. & Humbel, R. E., 1980. Nature 287:781–787.Google Scholar
  39. 39.
    Malaisse-Lagae, R., Carpentier, J. L., Patel, Y. C., Malaisse, W. J. & Orci, L., 1977. Experienta, 33: 915–917.Google Scholar
  40. 40.
    Gates, R. J. & Lazarus, N., 1977. Hormone Res. 8: 189–202.Google Scholar
  41. 41.
    Konopinska, D., Nawrocka, E., Siemion, I. Z., Szymaniec, S. & Slopek, S., 1979. Arch. Immunol. Therap. Exper. 27: 151–157.Google Scholar
  42. 42.
    Hisatsune, K., Kobayashi, K., Nozaki, S. & Muramatsu, I., 1978. Microbiol. Immunol. 22: 581–584.Google Scholar
  43. 43.
    Veretennikova, N. I., Indulen, Yu. I., Nikiforovich, G. V., Papsuyevich, O. S. & Chipens, G. I., 1978. 11th Int. S. Chem. Nat. Vol. 1, p. 263–266.Google Scholar
  44. 44.
    Veretennikova, N. L, Chipens, G. L, Nikiforovich, G. V. & Betinsh, Ya. R., 1980. Int. J. Peptide Protein Res. in press.Google Scholar

Copyright information

© Martinus Nijhoff/Dr W. Junk Publishers 1981

Authors and Affiliations

  • Victor A. Najjar
    • 1
  • Danuta Konopinska
    • 1
  • Manas K. Chaudhuri
    • 1
  • Donald E. Schmidt
    • 2
  • Lisa Linehan
    • 1
  1. 1.Division of Protein ChemistryTufts University, School of MedicineBostonUSA
  2. 2.Rainin Instruments Co., Inc.WoburnUSA

Personalised recommendations