Skip to main content
SpringerLink
Log in

Oligo(2′-O-methylribonucleotides) and their derivatives: IV. Conjugates of oligo(2′-O-methylribonucleotides) with minor groove binders and intercalators: Synthesis, properties, and application

  • Published:
Russian Journal of Bioorganic Chemistry Aims and scope Submit manuscript

Abstract

Triplex forming 3′-protected pyrimidine oligo(2′-O-methylribonucleotides) containing minor groove binders (MGB) and triplex specific intercalator, benzoindoloquinoline (BIQ), at the 5′-terminus were synthesized. The resulting conjugates formed stable complexes with a target dsDNA due to the simultaneous binding to the minor and major grooves and BIQ intercalation. The dissociation constants and the thermal stability were evaluated for the conjugate complexes with the model dsDNA corresponding to the polypurine tract (PPT) of the nef and pol genes from the HIV proviral genome. The conjugation of oligo(2′-O-methylribonucleotides) with MGB and BIQ was shown to increase the stability of the triple complexes with dsDNA at pH 7.2 and 37°C. Moreover, the intercalator accelerates the process of the complex formation. The dosedependent arrest of the in vitro transcription was demonstrated when a 780-bp DNA fragment containing the polypurine tract was transcribed under the control of T7 promoter in the presence of different concentrations of conjugates of oligo(2′-O-methylribonucleotides) containing MGB and BIQ.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

BIQ:

6-[(3-aminopropyl)amino]-11-methoxy-13H-benzo[6,7]indolo[3,2-c]quinoline

Cm :

2′-O-methylribo-cytidine

DMAP:

4-N,N′-dimethylaminopyridine

γ:

γ-ami-nobutyric acid

HEPES:

(4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid)

Im:

N-methylimidazole

MES:

2-(N-morpholino)ethanesulphonic acid

MGB:

minor groove binder

Nm :

2′-O-methylribonucleoside

Py :

N-methylpyrrole

inv T :

thymidine attached via 3′-3′-phosphodiester internucleotide bond (“inverted” thymidine)

TEA:

triethylamine

TFO:

triplexforming oligonucleotides

Um :

2′-O-methyluridine

References

  1. Novopashina D.S., Totskaya O.S., Kholodar S.A., Meschaninova M.I., Venyaminova.G, Russ. J. Bioorg. Chem., 2008, vol. 34, pp. 602–612.

    Article  CAS  Google Scholar 

  2. Malvy, C., Harel-Bellan, A., and Pritchard, L.L., Triple Helix Forming Oligonucleotides, Boston: Kluwer, 1999.

    Book  Google Scholar 

  3. Duca, M., Vekhoff, P., Oussedik, K., Halby, L., and Arimondo, P.B., Nucleic Acids Res., 2008, vol. 36, pp. 5123–5138.

    Article  PubMed  CAS  Google Scholar 

  4. Sanghvi, Y.S., Curr. Protoc. Nucleic Acid Chem., 2011, Chapter 4, Unit 4.1.1-22.

    Google Scholar 

  5. Bennett, C.F. and Swayze, E.E., Annu. Rev. Pharmacol. Toxicol., 2010, vol. 50, pp. 259–293.

    Article  PubMed  CAS  Google Scholar 

  6. Beban, M. and Miller, P.S., Biochem. Biophys. Acta, 2000, vol. 1492, pp. 155–162.

    Article  PubMed  CAS  Google Scholar 

  7. Torigoe, H., Shimizume, R., Sarai, A., and Shindo, H., Biochemistry, 1999, vol. 38, pp. 14653–14659.

    Article  PubMed  CAS  Google Scholar 

  8. Eder, P.S., DeVine, R.J., Dagle, J.M., and Walder, J.A., Antisense Res. Dev., 1991, vol. 1, pp. 141–151.

    PubMed  CAS  Google Scholar 

  9. Boutorine, A.S., Venyaminova, A.G., Repkova, M.N., Sergueyeva, Z.A., and Pyshnyi, D.V., Biochimie, 1994, vol. 76, pp. 23–32.

    Article  PubMed  CAS  Google Scholar 

  10. Novopashina, D.S., Totskaya, O.S., Lomzov, A.A., and Venyaminova, A.G., Nucleosides Nucleotides Nucleic Acids, 2005, vol. 24, pp. 527–531.

    Article  PubMed  CAS  Google Scholar 

  11. Giovannangeli, C., Perrouault, L., Escude, C., Thuong, N.T., and Hélène, C., Biochemistry, 1996, vol. 35, pp. 10539–10548.

    Article  PubMed  CAS  Google Scholar 

  12. Arimondo, P.B. and Hélène, C., Curr. Med. Chem., 2001, vol. 1, pp. 219–235.

    Article  CAS  Google Scholar 

  13. Bentin, T. and Nielsen, P.E., J. Am. Chem. Soc., 2003, vol. 125, pp. 6378–6379.

    Article  PubMed  CAS  Google Scholar 

  14. Silver, G.C., Nguyen, C.H., Boutorine, A.S., Bisagni, E., Garestier, T., and Hélène, C., Bioconj. Chem., 1997, vol. 8, pp. 15–22.

    Article  CAS  Google Scholar 

  15. Silver, G.C., Sun, J.S., Nguyen, C.H., Boutorine, A.S., Bisagni, E., and Hélène, C., J. Am. Chem. Soc., 1997, vol. 119, pp. 263–268.

    Article  CAS  Google Scholar 

  16. Nguyen, C.H., Marchand, C., Delage, S., Sun, J.S., Garestier, T., Hélène, C., and Bisagni, E., J. Am. Chem. Soc., 1998, vol. 120, pp. 2501–2507.

    Article  CAS  Google Scholar 

  17. Schmitt, P., Sun, J.S., Garestier, T., Hélène, C., Nguyen, C.H., Grierson, D.S., and Bisagni, E., Chem. Commun., 2000, pp. 763–764.

    Google Scholar 

  18. Sinyakov, A.N., Ryabinin, V.A., Grimm, G.N., and Boutorine, A.S., Mol. Biol. (Moscow), 2001, vol. 35, pp. 251–260.

    Article  CAS  Google Scholar 

  19. Szewczyk, J.W., Baird, E.E., and Dervan, P.B., Angew. Chem., Int. Ed. Engl., 1996, vol. 35, pp. 1487–1489.

    Article  CAS  Google Scholar 

  20. Novopashina, D., Sinyakov, A., Ryabinin, V., Venyaminova, A., and Boutorine, A., Nucleosides Nucleotides Nucleic Acids, 2003, vol. 22, pp. 1179–1182.

    Article  PubMed  CAS  Google Scholar 

  21. Dervan, P.B. and Burli, R.W., Curr. Opin. Chem. Biol., 1999, vol. 3, pp. 688–693.

    Article  PubMed  CAS  Google Scholar 

  22. Dervan, P.B. and Edelson, B.S., Curr. Opin. Struct. Biol., 2003, vol. 13, pp. 284–299.

    Article  PubMed  CAS  Google Scholar 

  23. Dervan, P.B., Poulin-Kerstein, A.T., Fechter, E.J., and Edelson, B.S., Top. Curr. Chem., 2005, vol. 253, pp. 1–31.

    CAS  Google Scholar 

  24. Novopashina, D.S., Sinyakov, A.N., Ryabinin, V.A., Venyaminova, A.G., Halby, L., Sun, J.-S., and Boutorine, A.S., Chem. Biodiv., 2005, vol. 2, pp. 936–952.

    Article  CAS  Google Scholar 

  25. Koroleva, O.N., Volkov, E.M., and Drutsa, V.L., Bioorg. Khim., 1994, vol. 20, pp. 420–432.

    PubMed  CAS  Google Scholar 

  26. Horn, S. and Schwenzer, B., Antisense Nucl. Acids Drug Dev., 1999, vol. 9, pp. 465–472.

    Article  CAS  Google Scholar 

  27. Garegg, P.J., Lindh, I., Regberg, T., Stawinski, J., Stromberg, R., and Henrichson, C., Tetrahedron Lett., 1986, vol. 27, pp. 4055–4058.

    Article  CAS  Google Scholar 

  28. Grimm, G.N., Boutorine, A.S., and Helene, C., Nucleosides Nucleotides Nucleic Acids, 2000, vol. 19, pp. 1943–1965.

    Article  PubMed  CAS  Google Scholar 

  29. Zarytova, V., Ivanova, E., and Venyaminova, A., Nucleosides Nucleotides, 1998, vol. 17, pp. 649–662.

    Article  CAS  Google Scholar 

  30. Ryabinin, V.A., Gorbunov, Yu.A., and Sinyakov, A.N., Russ. J. Bioorg. Chem, 1997, vol. 23, pp. 498–503.

    Google Scholar 

  31. Ryabinin, V.A. and Sinyakov, A.N., Russ. J. Bioorg. Chem., 1998, vol. 24, pp. 531–536.

    Google Scholar 

  32. Denisov, A.Yu., Ryabinin, V.A., Pyshnyi, D.V., Abramova, T.V., and Sinyakov, A.N., Zh. Strukt. Khim., 2001, vol. 34, pp. 111–119.

    Google Scholar 

  33. Giovannangeli, C., Diviacco, S., Labrousse, V., Gryaznov, S., Charneau, P., and Helene, C., Proc. Natl. Acad. Sci. USA, 1997, vol. 94, pp. 79–84.

    Article  PubMed  CAS  Google Scholar 

  34. Ryabinin, V.A., Denisov, A.Yu., Pyshnyi, D.V., Abramova, T.V., Sinyakov, A.N, and Vlasov, V.V., Dokl. Akad. Nauk SSSR, 1999, vol. 368, pp. 836–838.

    CAS  Google Scholar 

  35. Boutorine, A.S. and Escudé, C., Curr. Protoc. Nucleic Acid Chem., 2007, Chapter 7, Unit 7.12.

    Google Scholar 

  36. Giovannangeli, C., Perrouault, L., Escude, C., Gryaznov, S.M., and Hélène, C., J. Mol. Biol., 1996, vol. 261, pp. 386–398.

    Article  PubMed  CAS  Google Scholar 

  37. Brunet, E., Alberti, P., Perrouault, L., Babu, R., Wengel, J., and Giovannangeli, C., J. Biol. Chem., 2005, vol. 280, pp. 20076–20085.

    Article  PubMed  CAS  Google Scholar 

  38. Gordon, A.G. and Ford, R.A., The Chemist’s Companion, New York; London; Sydney; Toronto: A Wiley-Interscience Publication, 1972.

    Google Scholar 

  39. Sergeeva, Z.A., Lokhov, S.G., and Ven’yaminova, A.G., Russ. J. Bioorg. Chem., 1996, vol. 22, pp. 800–806.

    Google Scholar 

  40. Ramalho Ortigao, J.F., Rösch, H., Selter, H., Fröhlich, H., Lorenz, A., Montenarh, M., and Seliger, H., Antisense Res. Dev., 1992, vol. 2, pp. 129–146

    CAS  Google Scholar 

  41. Efimov, V.A., Buryakova, A.A., Reverdatto, S.V., and Chakhmakhcheva, O.G., Bioorg. Khim., 1983, vol. 9, pp. 1376–1381.

    Google Scholar 

  42. Borer, P.N., Handbook of Biochemistry and Molecular Biology, Fasman, G.D., Ed., Cleveland: CRC Press, 1975.

  43. Sinyakov, A.N., Ryabinin, V.A., Seregin, S.V., Lokhov, S.G., Kutyavin, I.V., Gamper, H.B., and Mayer, R.B., Russ. J. Bioorg. Chem., 1997, vol. 23, pp. 502–510.

    Google Scholar 

  44. Ryabinin, V.A., Boutorin, A.S., Helene, C., Denisov, A.Yu., Pyshnyi, D.V., and Sinyakov, A.N., Russ. J. Bioorg. Chem., 2005, vol. 31, pp. 146–152.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of RAS, pr. Lavrentieva 8, Novosibirsk, 630090, Russia

    D. S. Novopashina, A. N. Sinyakov, V. A. Ryabinin & A. G. Venyaminova

  2. Muséum National d’Histoire Naturelle (MNHN), CNRS UMR 7196, INSERM U565, 57, rue Cuvier, BP 26, 75231, Paris, cedex 05, France

    L. Perrouault, C. Giovannangeli & A. S. Boutorine

Authors
  1. D. S. Novopashina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. N. Sinyakov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. A. Ryabinin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Perrouault
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. Giovannangeli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. G. Venyaminova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. S. Boutorine
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. S. Novopashina.

Additional information

Original Russian Text © D.S. Novopashina, A.N. Sinyakov, V.A. Ryabinin, L. Perrouault, C. Giovannangeli, A.G. Venyaminova, A.S. Boutorine, 2013, published in Bioorganicheskaya Khimiya, 2013, Vol. 39, No. 2, pp. 159–174.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Novopashina, D.S., Sinyakov, A.N., Ryabinin, V.A. et al. Oligo(2′-O-methylribonucleotides) and their derivatives: IV. Conjugates of oligo(2′-O-methylribonucleotides) with minor groove binders and intercalators: Synthesis, properties, and application. Russ J Bioorg Chem 39, 138–152 (2013). https://doi.org/10.1134/S1068162013010081

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162013010081

Keywords

Search

Navigation