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Luliberin analogues containing the nuclear localization sequence of the SV-40 virus T-antigen

Russian Journal of Bioorganic Chemistry volume 36, pages 581–588 (2010)Cite this article

Abstract

With the goal of improving the efficacy of anticancer drugs due to the directed delivery to intracellular targets, a set of luliberin analogues containing the nuclear localization signal (NLS) of the SV-40 virus large T-antigen has been synthesized. The NLS was attached to the parent molecule via the D-lysine ɛ-amino group introduced into position 1 or 6 of the peptide sequence using the orthogonal protection strategy. Biological tests demonstrated that this modification supported in vitro a significant increase in the cytotoxic activity of luliberin analogues containing palmitoyl residues. The influence of the studied peptides on tumor cells was not associated with the distortion of the membrane integrity, which was confirmed by experiments with normal fibroblasts used as a control.

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Abbreviations

ATCC:

American typical culture collection

Bzl(Cl2):

2,6-dichlorobenzyl

DMEM:

Dulbecco’s modified Eagle medium

GnRH:

luliberin

Mts:

mesitylenesulfonyl

NLS:

nuclear localization signal

Pam:

palmitoyl

PBS:

phosphate buffer solution

TFMSA:

trifluoromethanesulfonic acid

TEA:

triethylamine

Trt:

triphenylmethyl

Z(Cl):

2-chloromethyloxycarbonyl

RCCC:

Russian cell culture collection

References

  1. Corbin, A., Yale J. Biol. Med., 1982, vol. 55, no. 1, pp. 27–47.

    CAS  PubMed  Google Scholar 

  2. Redding, T.W., Coy, D.H., and Schally, A.V., Proc. Natl. Acad. Sci. USA, 1982, vol. 79, no. 4, pp. 1273–1276.

    CAS  Article  PubMed  Google Scholar 

  3. Tolis, G., Ackman, D., Stellos, A., Mehta, A., Labrie, F., Fazekas, A.T., Comaru-Schally, A.M., and Schally, A.V., Proc. Natl. Acad. Sci. USA, 1982, vol. 79, no. 5, pp. 1658–1662.

    CAS  Article  PubMed  Google Scholar 

  4. Nechushtan, A., Yarkoni, S., Marianovsky, I., and Lorberboum-Galski, H., J. Biol. Chem., 1997, vol. 272, pp. 11597–11603.

    CAS  Article  PubMed  Google Scholar 

  5. Schally, A.V. and Nagy, A., Eur. J. Endocrinol., 1999, vol. 141, no. 1, pp. 1–14.

    CAS  Article  PubMed  Google Scholar 

  6. Schally, A.V., Nagy, A., Szepeshazi, K., Pinski, J., Halmos, G., Armatis, P., Miyazaki, M., Comaru-Schally, A.M., Yano, T., and Emons, G., in LH-RH Analogs with Cytotoxic Radicals, Filicori, M. and Flamigni, C., Eds., Carnforth, UK: Parthenon Publishing, 1996, pp. 33–44.

    Google Scholar 

  7. Rahimipour, S., Weiner, L., Shrestha-Dawadi, P.B., Bittner, S., Koch, Y., and Fridkin, M., Lett. Pept. Sci., 1998, vol. 5, nos. 5–6, pp. 421–427.

    CAS  Google Scholar 

  8. Rahimipour, S., Bilkis, I., Peron, V., Gescheidt, G., Barbosa, F., Mazur, Y., Koch, Y., Weiner, L., and Fridkin, M., Photochem. Photobiol., 2001, vol. 74, no. 2, pp. 226–236.

    CAS  Article  PubMed  Google Scholar 

  9. Rahimipour, S., Ben-Aroya, N., Ziv, K., Chen, A., Fridkin, M., and Koch, Y., J. Med. Chem., 2003, vol. 46, no. 19, pp. 3965–3974.

    CAS  Article  PubMed  Google Scholar 

  10. Lev-Goldman, V., Mester, B., Ben-Aroya, N., Koch, Y., Weiner, L., and Fridkin, M., Bioconjug. Chem., 2006, vol. 17, no. 4, pp. 1008–1016.

    CAS  Article  PubMed  Google Scholar 

  11. Szende, B., Srkalovic, G., Timar, J., Mulchahey, J.J., Neill, J.D., Lapis, K., Csikos, A., Szepeshazi, K., and Schally, A.V., Proc. Natl. Acad. Sci. USA, 1991, vol. 88, no. 10, pp. 4153–4156.

    CAS  Article  PubMed  Google Scholar 

  12. Cornea, A., Janovick, J.A., Lin, X., and Conn, P.M., Endocrinology, 1999, vol. 140, no. 9, pp. 4272–4280.

    CAS  Article  PubMed  Google Scholar 

  13. Morel, G., Dihl, F., Aubert, M.L., and Dubois, P.M., Cell Tissue Res., 1987, vol. 248, no. 3, pp. 541–550.

    CAS  Article  PubMed  Google Scholar 

  14. Sanchez, C., Clementi, M., Benitez, D., Contreras, H., Huidobro, C., and Castellon, E., The Prostate, 2005, vol. 65, no. 3, pp. 195–202.

    CAS  Article  PubMed  Google Scholar 

  15. LaCasse, E.C. and Lefebvre, Y.A., Nucleic Acids Research, 1995, vol. 23, no. 10, pp. 1647–1656.

    CAS  Article  PubMed  Google Scholar 

  16. Conti, E., Uy, M., Leighton, L., Blobel, G., and Kuriyan, J., Cell, 1998, vol. 94, no. 2, pp. 193–204.

    CAS  Article  PubMed  Google Scholar 

  17. Ogris, M., Carlisle, R.C., Bettinger, T., and Seymour, L.W., J. Biol. Chem., 2001, vol. 276, no. 50, pp. 47550–47555.

    CAS  Article  PubMed  Google Scholar 

  18. Standiford, D.M. and Richter, J.D., J. Cell Biol., 1992, vol. 118, no. 5, pp. 991–1002.

    CAS  Article  PubMed  Google Scholar 

  19. Kalderon, D., Richardson, W.D., Markham, A.F., and Smith, A.E., Nature, 1984, vol. 311, no. 5981, pp. 33–38.

    CAS  Article  PubMed  Google Scholar 

  20. Burov, S.V., Yablokova, T.V., Dorosh, M.Yu., Shkarubskaya, Z.R., Blank, M., Epstein, N., and Fridkin, M., Bioorg. Khim., 2006, vol. 32, pp. 459–466 [Russ. J. Bioorg. Chem. (Eng. Transl.), 2006, vol. 32, pp. 413–419].

    CAS  PubMed  Google Scholar 

  21. Nishio, H., Nishiuchi, Y., Ishimaru, M., and Kimura, T., Int. J. Pept. Res. Ther., 2003, vol. 10, nos. 5–6, pp. 589–596.

    CAS  Article  Google Scholar 

  22. Bonilla, E. and del Mazo, J., Biochem. Pharmacol., 2003, vol. 65, no. 5, pp. 1701–1707.

    CAS  Article  PubMed  Google Scholar 

  23. Keisari, Y., J. Immunol. Methods, 1992, vol. 146, pp. 155–161.

    CAS  Article  PubMed  Google Scholar 

  24. Burov, S. and Epstein, N., Peptides Useful for Treating GnRH Associated Diseases, WO 2005/116058, Priority date May 27, 2004.

  25. Yang, W.-H., Wieczorck, M., Allen, M.C., and Nett, T.M., Endocrinology, 2003, vol. 144, no. 4, pp. 1456–1463.

    CAS  Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Macromolecular Compounds, Russian Academy of Sciences, Bol’shoi proezd 31, St. Petersburg, 119004, Russia

    S. V. Burov, T. V. Yablokova, M. Yu. Dorosh & E. V. Krivizyuk

  2. St. Petersburg State University, St. Petersburg, Russia

    A. M. Efremov

  3. Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia

    S. V. Orlov

Authors
  1. S. V. Burov
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  2. T. V. Yablokova
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  3. M. Yu. Dorosh
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  4. E. V. Krivizyuk
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  5. A. M. Efremov
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  6. S. V. Orlov
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Corresponding author

Correspondence to S. V. Burov.

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Original Russian Text © S.V. Burov, T.V. Yablokova, M.Yu. Dorosh, E.V. Krivizyuk, A.M. Efremov, S.V. Orlov, 2010, published in Bioorganicheskaya Khimiya, 2010, Vol. 36, No. 5, pp. 630–637.

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Burov, S.V., Yablokova, T.V., Dorosh, M.Y. et al. Luliberin analogues containing the nuclear localization sequence of the SV-40 virus T-antigen. Russ J Bioorg Chem 36, 581–588 (2010). https://doi.org/10.1134/S1068162010050055

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  • DOI: https://doi.org/10.1134/S1068162010050055

Key words

  • anticancer activity
  • luliberin
  • nuclear localization signal
  • palmitic acid