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Immunotoxins pp 281-295 | Cite as

Hormone, lectin and toxin-toxin conjugates

  • Thomas N. Oeltmann
  • Ronald G. Wiley
Part of the Cancer Treatment and Research book series (CTAR, volume 37)

Abstract

In order to better understand the relative importance of the A and B chains of diphtheria toxin and ricin, chimeras or hybrid toxins have been constructed with diphtheria toxin subunits and ricin subunits coupled to a number of different binding moieties. These experiments have demonstrated wide variations in cytotoxicity depending on the specific combinations of A chain and binding moiety.

Keywords

Insulin Receptor Cholera Toxin Diphtheria Toxin Hybrid Molecule Placental Lactogen 
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.

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References

  1. 1.
    Gilliland, D.G., Collier, R.J., Moehring, J.M., and Moehring, T.J. (1978) Chimeric toxins: Toxic disulfide-linked conjugate of concanavalin A with fragment A from diphtheria toxin. Proc. Natl. Acad. Sci. USA, 75, 5319–5323.PubMedCrossRefGoogle Scholar
  2. 2.
    Gilliland, D.G., and Collier, R.J., (1980) A model system involving anticoncanavalin A antibody targeting of diphtheria toxin fragment A. Cancer Res., 40, 3564–3569.PubMedGoogle Scholar
  3. 3.
    Gilliland, D.G., and Collier, R.J. (1981) Characterization of hybrid molecules containing fragment A from diphtheria toxin linked to concanavalin A or the binding subunit of ricin toxin. J. Biol. Chem., 256, 12731–12739.PubMedGoogle Scholar
  4. 4.
    Gilliland, D.G., Mannhalter, J., and Collier, R.J. (1981) Chimeric toxins containing fragment A from diphtheria toxin. In: Receptor-Mediated Binding and Internalization of Toxins and Hormones. J.L. Middlebrook, and L.D. Kohn, eds. Academic Press, New York, pp 311–327.Google Scholar
  5. 5.
    Guillemot, J.C., Sundan, A., Olsens, S., and Sandvig, K. (1985) Entry of diphtheria toxin linked to concanavalin A into primate and murine cells. J. Cell. Physiol., 122, 193–199.PubMedCrossRefGoogle Scholar
  6. 6.
    Youle, R.J., and Neville, D.M., Jr. (1979) Receptor-mediated transport of the hybrid protein ricin-diphtheria toxin fragment A with subsequent ADP-ribosylation of intracellular elongation factor II. J. Biol. Chem., 254, 11089–11096.PubMedGoogle Scholar
  7. 7.
    Uchida, T., Yamaizumi, M., and Okada, Y. (1978) Formation of a hybrid toxin from ricin agglutinin and a non-toxic mutant protein of diphtheria toxin. Biochem. Biophys, Res. Comm., 81, 268–273.Google Scholar
  8. 8.
    Sundan, A., Olsnes, S., Sandvig, K., and Pihl, A. (1982) Preparation and properties of chimeric toxins prepared from the constituent polypeptides of diphtheria toxin and ricin. Evidence for entry of ricin A-chain via the diphtheria toxin pathway. J. Biol. Chem., 257, 9733–9739.PubMedGoogle Scholar
  9. 9.
    Mannhalter, J.W., Gilliland, D.S., and Collier, R.J. (1980) A hybrid toxin containing fragment A from diphtheria toxin linked to the B protomer of cholera toxin. Biochim. Biophys. Acta, 626, 443–450.PubMedGoogle Scholar
  10. 10.
    Uchida, T., Yamaizumi, M., Mekada, E., Okada, Y., Tsuda, M., Kurokawa, T., and Sugion, Y. (1978) Reconstitution of hybrid toxin from fragment A of diphtheria toxin and a subunit of Wisteria floribunda lectin. J. Biol. Chem., 253, 6307–6310.PubMedGoogle Scholar
  11. 11.
    Olsnes, S., Pappenheimer, A.M., and Meren R. (1974) Lectins from Abrus precatorius and Ricinus communis II. Hybrid toxins and their interaction with chain-specific antibodies. J. Immunol., 113, 842–847.PubMedGoogle Scholar
  12. 12.
    Sundan, A., Sandvig, K., and Olsnes, S. (1983) Preparation and properties of a hybrid toxin of modeccin A-chain and ricin B-chain. Biochim. Biophys. Acta, 761, 296–302.PubMedGoogle Scholar
  13. 13.
    Yamaguchi, T., Kato, R., Beppu, M., Terao, T., Inoue, Y., Ikawa, Y., and Osawa, T. (1979) Preparation of concanavalin A-ricin A-chain conjugate and its biologic activity against various cultured cells. J. Nat. Cancer Inst., 62, 1387–1395.PubMedGoogle Scholar
  14. 14.
    Yamaguchi, T., Beppu, M., Terao, T., and Osawa, T. (1982) Different cytoxicity of ricin and a concanavalin A-ricin A-chain conjugate between Balb/c 3T3 cells and the transformed cells. J. Pharm. Dyn., 5, 678–685.Google Scholar
  15. 15.
    Uchida, T., Mekada, E., and Okada, Y. (1980) Hybrid toxin of the A chain of ricin toxin and a subunit of Wisteria floribunda lectin. Possible importance of the hydrophobic region for entry of toxin into the cell. J. Biol. Chem., 255, 6687–6693.PubMedGoogle Scholar
  16. 16.
    Oeltman, T.N., and Wiley, R.G. (1986) Wheat germ agglutinin-ricin A-chain conjugate is neuronotoxic after vagal injection. Brain Res., 377, 221–228.CrossRefGoogle Scholar
  17. 17.
    Delfini, C., Sargiacomo, M., Amici, C., Oberholtzer, G., and Tomasi, M. (1982) Cholera toxin B-subunit protects mammalian cells from ricin and abrin toxicity. J. Cell. Biochem., 20, 359–367.PubMedCrossRefGoogle Scholar
  18. 18.
    Stirpe, F., Olsnes, S., and Pihl, A. (1980) Gelonin, a new inhibitor of protein synthesis, nontoxic to intact cells. Isolation, characterization and preparation of cytotoxic complexes with concanavalin A. J. Biol. Chem., 255, 6947–6953.PubMedGoogle Scholar
  19. 19.
    Kahn, C.R. (1976) Membrane receptors for hormone and neurotransmitters. J. Cell Biol., 70, 261–286.PubMedCrossRefGoogle Scholar
  20. 20.
    Kahn, C.R. (1979) What is the molecular basis for the action of insulin? Trends Biochem. Sci., 4, 263–266.CrossRefGoogle Scholar
  21. 21.
    Massague, J., Pilch, P.F., and Czech, M.P. (1980) Electrophoretic resolution of three major insulin receptor structures with unique subunit stoichiometries. Proc. Natl. Acad. Sci. USA, 77, 7137–7141.PubMedCrossRefGoogle Scholar
  22. 22.
    Goldfine, I.D., Roth, R.A., Wong, K.Y., and Iwamoto, Y. (1981) Internalization of insulin into liver: Biological significance. In: Serono Symposium No. 41, Current Views on Insulin Receptors. R. De Pirro, R. Lauro, J. Olefsky, and J. Roth, eds.) Academic Press, New York, pp 167–180.Google Scholar
  23. 23.
    Massague, J., and Czech, M.P. (1982) The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptors. J. Biol. Chem., 257, 5038–5045.PubMedGoogle Scholar
  24. 24.
    White, M.F., Haring, H.-U., Kasuga, M., and Kahn, R.C. (1984) Kinetic properties and sites of autophosphorylation of the partially purified insulin receptor from hepatoma cells. J. Biol. Chem., 259, 255–264.PubMedGoogle Scholar
  25. 25.
    Jacobs, S., and Cautrecasas, P. (1983) Insulin receptors. Ann. Rev. Pharmacol. Toxicol., 23, 461–479.CrossRefGoogle Scholar
  26. 26.
    Schweitzer, J.B., Smith, R.M., and Jarett, L. (1980) Difference in organizational structure of insulin receptors on rat adipocyte and liver plasma membranes: Role of disulfide bonds. Proc. Natl. Acad. Sci. USA, 77, 4692–4696.PubMedCrossRefGoogle Scholar
  27. 27.
    Terris, S., and Steiner D.F. (1980) Insulin-receptor turnover and down regulation. In: Insulin: Chemistry, Structure, and Function of Insulin and Related Hormone. Proceedings of Second International Symposium. D. Brandenburg, A. Wollmer, and W. DeGruyter, eds. DeGruyter, Berlin, pp 277–284.Google Scholar
  28. 28.
    Krupp, M.N., and Lane, M.D. (1982) Evidence for different pathways for the degradation of insuli and insulin receptor in the chick liver cell. J. Biol. Chem., 257, 1372–1377.PubMedGoogle Scholar
  29. 29.
    Marshall, S., Green, A., and Olefsky, J.M. (1981) Evidence for recycling of insulin receptors in isolated rat adipocytes. J. Biol. Chem., 256, 11464–11470.PubMedGoogle Scholar
  30. 30.
    Goldfine, I.D. (1981) Interaction of insulin, polypeptide hormones, and growth factors with intracellular membranes. Biochem. Biophys. Acta, 650, 53–67.PubMedGoogle Scholar
  31. 31.
    Walaas, O., and Horn, R.S. (1981) The controversial problem of insulin action. Trends Pharmacol. Sci., 2, 196–198.CrossRefGoogle Scholar
  32. 32.
    Roth, R.A., Maddux, B.A., Wong, K.Y., Iwamoto, Y., and Goldfine, I.D. (1981) Insulin-ricin B chain conjugate. J. Biol. Chem., 256, 5350–5354.PubMedGoogle Scholar
  33. 33.
    Hofmann, C.A., Lotan, R.M., Ku, W.W., and Oeltmann, T.N. (1983) Insulin-ricin B hybrid molecule mediates an insulin associated effect on cells which do not bind insulin. J. Biol. Chem., 258, 11774–11779.PubMedGoogle Scholar
  34. 34.
    Hofmann, C.A., Lotan, R.M., Rath, G.D., and Oeltmann, T.N. (1983) Insulin-ricin B hybrid molecules: Receptor binding and biological activity in a minimal deviation hepatoma cell line. Arch. Biochem. Biophys., 227, 448–456.PubMedCrossRefGoogle Scholar
  35. 35.
    Roth, R.A., Iwamoto, Y., Maddux, B., and Goldfine, I.D. (1983) Insulin-ricin B chain conjugate has enhanced biological activity in insulin-insensitive cells. Endocrinology, 112, 2193–2199.PubMedCrossRefGoogle Scholar
  36. 36.
    Roth, R.A., and Maddux, B. (1983) Insulin-cholera toxin binding subunit conjugate: A hybrid molecule with insulin biological activity and cholera toxin binding specificity. J. Cell. Phys., 115, 151–158.CrossRefGoogle Scholar
  37. 37.
    Miskimins, W.K., and Shimizu, N. (1979) Synthesis of a cytotoxic insulin cross-linked to diphtheria toxin fragment A capable of recognizing insulin receptors. Biochem. Biophys. Res. Comm., 91, 143–151.PubMedCrossRefGoogle Scholar
  38. 38.
    Shimizu, Y., and Shimizu, N. (1986) Rat hepatoma cell variants resistant to insulin-diphtheria toxin fragment A conjugates. J. Biol. Chem., 261, 7342–7346.PubMedGoogle Scholar
  39. 39.
    Simpson, D.L., Cawley, D.B., and Herschman, H.R. (1982) Killing of cultured hepatocytes by conjugates of asialofetuin and EGT linked to the A chains of ricin and diphtheria toxin. Cell, 29, 469–473.PubMedCrossRefGoogle Scholar
  40. 40.
    Miskimins, W.K., and Shimizu, N. (1981) Genetics of cell surface receptors for bioactive polypeptides: Variants of Swiss/3T3 fibroblast resistant to a cytotoxic chimeric insulin. Proc. Natl. Acad. Sci. USA, 78, 445–449.PubMedCrossRefGoogle Scholar
  41. 41.
    Sandvig, K., and Olsnes, S. (1981) Rapid entry of nicked diphtheria toxin into cells at low pH. J. Biol. Chem., 256, 9068–9076.PubMedGoogle Scholar
  42. 42.
    Bacha, P., Murphy, J.R., and Reichlin, S. (1983) Thyrotropin-releasing hormone diphtheria toxin-related polypeptide conjugates. J. Biol. Chem., 258, 1565–1570.PubMedGoogle Scholar
  43. 43.
    Holmes, R.K. (1976) Characterization and genetic mapping of nontoxinogenic mutants of corynebacteriophage beta. J. Virol., 19, 195–207.PubMedGoogle Scholar
  44. 44.
    Uchida, T., Gill, D.M., and Pappenheimer, A.M., Jr. (1971) Mutation in the structural gene for diphtheria toxin carried by a temperature phage. Nature New Biol., 233, 8–11.PubMedCrossRefGoogle Scholar
  45. 45.
    Hinkle, P.M., and Tashjian, A.H. Receptors for (1973) thyrotropin-releasing hormone in prolactin-producing rat pituitary cells in culture. J. Biol. Chem., 248, 6180–6186.Google Scholar
  46. 46.
    Kagen, B.L., Finkelstein, A., and Colombini, M. (1981) Diphtheria toxin fragment forms large pores in phospholipid bilayer membranes, Proc. Natl. Acad. Sci. USA, 78, 4950–4954.CrossRefGoogle Scholar
  47. 47.
    Chang, T., and Neville, D.M., Jr. (1977) Artificial hybrid protein containing a toxic protein fragment and a cell membrane receptor-binding moiety in a disulfide conjugate. I. Synthesis of a diphtheria toxin fragment A-S-S-Human placental lactogen with Methyl-Sbromovalerimidate. J. Biol. Chem., 252, 1505–1514.PubMedGoogle Scholar
  48. 48.
    Chang, T., Dazord, A., and Neville, D.M., Jr. (1977) Artificial hybrid protein containing a toxic protein fragment and a cell membrane receptor-binding moiety in a disulfide conjugate. II. Biochemical and biologic properties of diphtheria toxin fragment A-S-S-human placental lactogen. J. Biol. Chem., 252, 1515–1522.PubMedGoogle Scholar
  49. 49.
    Oeltmann, T.N., and Heath, E.C. (1979) A hybrid protein containing the toxic subunit of ricin and the cell-specific subunit of human chorionic gonadotropin. I. Synthesis and characterization. J. Biol. Chem., 254, 1022–1027.PubMedGoogle Scholar
  50. 50.
    Oeltmann, T.N., and Heath, E.C. (1979) A hybrid protein containing the toxic subunit of ricin and the cell-specific subunit of human chorionic gonadotropin. II. Biologic properties. J. Biol. Chem., 254, 1028–1032.PubMedGoogle Scholar
  51. 51.
    Oeltmann, T.N. (1985) Synthesis and in vitro activity of a hormone-diphtheria toxin fragment A hybrid. Biochem. Biophys. Res. Comm., 133, 4430–4435.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1988

Authors and Affiliations

  • Thomas N. Oeltmann
  • Ronald G. Wiley

There are no affiliations available

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