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Artificial Proteins with Antiviral Properties of α-Interferons

Abstract

Consensus 30–36 sequence LKDRHDF of human α-interferons is inserted into the C- and N-terminal sequences of the artificial protein albeferon using genetic engineering methods in order to obtain artificial proteins with antiviral activity. Albeferon, obtained by Dolgikh et al. (Protein Eng., 1996, vol. 9, pp. 195–201), already contains the IFN-α 130–137 fragment and possesses antiproliferative activity comparable with that of IFN-α2. According to CD spectroscopy, both proteins have regular secondary structures similar to that of the precursor protein. They exhibit antiviral activities, and the activity of one of them is comparable with that of IFN-α2. At the same time, their cytotoxic properties are displayed only at relatively high concentrations, which substantially exceed the minimal antiviral concentrations.

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References

  1. Taniguchi, T., Mantei, N., Schwarztein, M., Nagata, S., Murmatsu, M., and Weissmann, C., Nature (London), 1980, vol. 285, pp. 547–549.

    Google Scholar 

  2. Pestka, S., Langer, J., Zoon, K., and Samuel, C., Annu. Rev. Biochem., 1987, vol. 56, pp. 727–777.

    Google Scholar 

  3. Uze, G., Lutfalla, G., and Mogensen, K., Cell (Cambridge, Mass.), 1990, vol. 60, pp. 225–234.

    Google Scholar 

  4. Novick, D., Cohen, B., and Rubinstein, M., Cell (Cambridge, Mass.), 1994, vol. 77, pp. 391–400.

    Google Scholar 

  5. Cohen, B., Novick, D., Barak, S., and Rubinstein, M., Mol. Cell. Biol., 1995, vol. 15, pp. 4208–4214.

    Google Scholar 

  6. Zav'yalov, V., Denesyuk, A., and Zav'yalova, G., Acta Pathol. Microbiol. Immunol. Scand., 1997, vol. 105, pp. 161–186.

    Google Scholar 

  7. Radhakrishnan, R., Walter, L., Hruza, A., Reichert, P., Trotta, P., Nagabhushan, T., and Walter, M., Structure, 1996, vol. 4, pp. 1453–1463.

    Google Scholar 

  8. Klaus, W., Gsell, B., Labhardt, A., Wipf, B., and Senn, H., J. Mol. Biol., 1997, vol. 274, pp. 661–675.

    Google Scholar 

  9. Zav'yalov, V. and Denesyuk, A., Immunol. Lett., 1982, vol. 4, pp. 7–14.

    Google Scholar 

  10. Zav'yalov, V., Denesyuk, A., and Zav'yalova, G., Immunol. Lett., 1989, vol. 22, pp. 173–182.

    Google Scholar 

  11. Zav'yalov, V., Denesyuk, A., and Zav'yalova, G., Biochim. Biophys. Acta, 1990, vol. 1041, pp. 178–185.

    Google Scholar 

  12. Sprang, S. and Bazan, J., Curr. Opin. Struct. Biol., 1993, vol. 3, pp. 815–827.

    Google Scholar 

  13. Barasoain, I., Portoles, A., Aramburu, J., and Rojo, J., J. Immunol., 1989, vol. 143, pp. 507–512.

    Google Scholar 

  14. Kontsek, P., Boresky, L., Kontsekova, E., Macicova, I., Kolsunova, A., Novak, M., and Krchnak, V., Mol. Immunol., 1991, vol. 28, pp. 1289–1297.

    Google Scholar 

  15. Kontsek, P., Boresky, L., Kontsekova, E., Kolsunova, A., Novak, M., Zav'yalov, V., and Maiorov, V., Mol. Immunol., 1992, vol. 29, pp. 863–870.

    Google Scholar 

  16. Kontsek, P., Boresky, L., Zav'yalov, V., and Maiorov, V., Immunol. Lett., 1993, vol. 35, pp. 281–284.

    Google Scholar 

  17. Zav'yalov, V., Navolotskaya, E., Abramov, V., Galaktionov, V., Isaev, I., Kaurov, O., Kozhich, A., Maiorov, V., Prusakov, A., Vasilenko, R., and Volodina, E., FEBS Lett., 1991, vol. 78, pp. 187–189.

    Google Scholar 

  18. Danilkovich, A., Freze, K., Shevalier, A., Samukov, V., Kirkin, A., and Gusev, M., Immunol. Lett., 1992, vol. 31, pp. 15–20.

    Google Scholar 

  19. Zav'yalov, V., Navolotskaya, E., Vasilenko, R., Abramov, V., Volodina, E., Roslovtseva, O., Prusakov, A., and Kaurov, O., Mol. Immunol., 1995, vol. 32, pp. 425–431.

    Google Scholar 

  20. Danilkovich, A., Freze, K., Romashkova, J., Valujskikh, A., Makarov, E., Targoni, O., Makarova, N., and Kushch, A., FEBS Lett., 1995, vol. 369, pp. 161–164.

    Google Scholar 

  21. Zav'yalov, V., Vasilenko, R., Dolgikh, D., Kirpichnikov, M., Navolotskaya, E., and Korpela, T., Intern. Patent Appl. PCT/FI98/00418, 2000, Finnish Patent WO9852594, 2001.

  22. Fish, E.N., J. Interferon Res., 1992, vol. 12, pp. 257–266.

    Google Scholar 

  23. Senda, T., Saitoh, S., and Mitsui, Y., J. Mol. Biol., 1995, vol. 253, pp. 187–207.

    Google Scholar 

  24. Piehler, J. and Schreiber, G., J. Mol. Biol., 1999, vol. 294, pp. 223–237.

    Google Scholar 

  25. Mitsui, Y., Senda, T., Shimazu, T., Matsuda, S., and Utsumi, J., Pharmacol. Ther., 1993, vol. 58, pp. 93–132.

    Google Scholar 

  26. Uze, G., Lutfalla, G., and Mogensen, K., J. Interferon Cytokine Res., 1995, vol. 15, pp. 3–26.

    Google Scholar 

  27. Fedorov, A., Dolgikh, D., Chemeris, V., Chernov, B., Finkelstain, A., Schulga, A., Alakhov, Y., Kirpichnikov, M., and Ptitsyn, O., J. Mol. Biol., 1992, vol. 225, pp. 927–931.

    Google Scholar 

  28. Dolgikh, D., Gabrielyan, A., Navolotskaya, E., Chemeris, V., and Kirpichnikov, M., Biofizika, 1993, vol. 35, pp. 67–74.

    Google Scholar 

  29. Aphsizheva, I., Dolgikh, D., Abdullaev, Z., Uversky, V., Kirpichnikov, M., and Ptitsyn, O., FEBS Lett., 1998, vol. 425/1, pp. 101–104.

    Google Scholar 

  30. Dolgikh, D., Uversky, V., Gabrielyan, A., Chemeris, V., Fedorov, A., Navolotskaya, E., Zav'yalov, V., and Kirpichnikov, M., Protein Eng., 1996, vol. 9, pp. 195–201.

    Google Scholar 

  31. Bogdan, C., Curr. Opin. Immunol., 2000, vol. 12, pp. 419–424.

    Google Scholar 

  32. Akbar, A., Lord, J., and Salmon, M., Immunol. Today, 2000, vol. 21, pp. 337–342.

    Google Scholar 

  33. Sinigaglia, F., D'Ambrosio, D., Panina-Bordignon, P., and Rogge, L., Immunol. Rev., 1999, vol. 170, pp. 65–72.

    Google Scholar 

  34. Santini, S., Lapenta, C., Logozzi, M., Parlato, S., Spada, M., Di Pucchio, T., and Belardelli, F., J. Exp. Med., 2000, vol. 191, pp. 1777–1788.

    Google Scholar 

  35. Ruuth, K., Carlsson, L., Hallberg, B., and Lundgren, E., Biochem. Biophys. Res. Commun., 2001, vol. 284, pp. 583–586.

    Google Scholar 

  36. Ronnblom, L., Alm, G., and Oberg, K., Ann. Intern. Med., 1991, vol. 115, pp. 178–183.

    Google Scholar 

  37. Ioannou, Y. and Isenberg, D., Arthritis Rheum., 2000, vol. 43, pp. 1431–1442.

    Google Scholar 

  38. Ronnblom, L. and Alm, G., J. Exp. Med., 2001, vol. 194, pp. 59–63.

    Google Scholar 

  39. Chertkova, R.V., Kostanyan, I.A., Astapova, M.V., Surina, E.A., Dolgikh, D.A., and Kirpichnikov, M.P., Bioorg. Khim., 2003, vol. 29, pp. 30–37.

    Google Scholar 

  40. Provencher, S. and Glocker, J., Biochemistry, 1981, vol. 20, p. 33.

    Google Scholar 

  41. Ershov, F., Sistema interferona v norme i pri patologii (Interferon System in Norm and Pathology), Moscow: Meditsyna, 1996, pp. 87–88.

    Google Scholar 

  42. Chizhov, N., Ershov, F., and Indulen, M., Osnovy eksperimental'noi khimioterapii virusnykh infektsii (Basics of Experimental Chemotherapy of Viral Infections), Riga: Zinatne, 1988, pp. 52–55.

    Google Scholar 

  43. Day, C., Schwartz, B., Li, B., and Pestka, S., J. Interferon Res., 1992, vol. 12, pp. 139–143.

    Google Scholar 

  44. Hu, R., Bekisz, J., Hayes, M., Audet, S., Beeler, J., Petricoin, E., and Zoon, K., J. Immunol., 1999, vol. 163, pp. 854–860.

    Google Scholar 

  45. Sambrook, J., Fritsch, E.F., and Maniatis, T., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor, N.Y.: Cold Spring Harbor Lab., 1989, pp. 389–412.

    Google Scholar 

  46. Practical Protein Chemistry: A Handbook, Darbre, A., Ed., Singapore: John Wiley and Sons Ltd, 1986, pp. 300–302.

    Google Scholar 

  47. Laemmli, U., Nature (London), 1970, vol. 227, pp. 680–685.

    Google Scholar 

  48. Schagger, H. and Jagow, G., Anal. Biochem., 1987, vol. 166, pp. 368–379.

    Google Scholar 

  49. Edman, P. and Henschen, A., Protein Sequence Determination, Needleman, S.B., Ed., Berlin: Springer, 1975, pp. 232–279.

    Google Scholar 

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Correspondence to R. V. Chertkova.

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Chertkova, R.V., Abdullaev, Z.K., Dolgikh, D.A. et al. Artificial Proteins with Antiviral Properties of α-Interferons. Russian Journal of Bioorganic Chemistry 29, 231–241 (2003). https://doi.org/10.1023/A:1023980331610

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  • DOI: https://doi.org/10.1023/A:1023980331610

  • albebetin
  • albeferon
  • α2-interferon
  • antiviral activity
  • artificial proteins