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Oligonucleotide analogues containing a C3′-NH-C(O)-CH2-C5′ amide internucleotide bond

Abstract

A dinucleotide containing a C3′-NH-C(O)-CH2-C5′ amide internucleotide bond was synthesized by the interaction of 3′-deoxy-3′-amino-5′-O-(tert-butyldimethylsilyl)thymidine with 3′-O-benzyl-2′-O-tert-butyldimethylsilyl-5′-deoxy-5′-carboxymethylribosylthymine, which was obtained from 2′-O-acetyl-3′-O-benzyl-5′-deoxy-5′-ethoxycarbonylmethylribosylthymine through the methanolysis of the acetyl group followed by silylation of liberated hydroxyl and ester saponification. After standard manipulation with protecting groups, the dinucleotide was converted into 3′-O(2-cyanoethyl-N,N-diisopropylphosphoramidite), which was used for the synthesis of modified oligonucleotides on an automated synthesizer. The melting curves of the duplexes formed by modified and complementary natural oligonucleotides were registered, and the melting temperatures and thermodynamic parameters of the duplex formation were calculated. The introduction of a single modified bond into the oligonucleotide led to an insignificant decrease in the melting temperature of these duplexes as compared to unmodified ones.

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Abbreviations

Bn:

benzyl

DIPEA:

diisopropylethylamine

TBDMS-Cl:

tert-butyldimethylsilyl chloride

TEAA:

triethylammonium acetate

(MeO)2Tr:

dimethoxytrityl

TFA:

trifluoroacetic acid

THF:

tetrahydrofuran

TBAF:

tetrabutylammonium fluoride

cT:

5′-deoxy-5′-carboxymethyl-5′-ribosylthymine

Ta:

3′-amino-3′-deoxythymidine

References

  1. Crooke, S.T, in Antisense Drug Technology: Principles, Strategies and Application, Second ed., Crooke, S.T., Ed., New York: Marcel Dekker, 2007, pp. 1–19.

    Google Scholar 

  2. Wilton, S.D. and Fletcher, S., Curr. Gene Ther., 2005, vol. 5, pp. 467–483.

    Article  CAS  PubMed  Google Scholar 

  3. Leonetti, C. and Zupi, G., Curr. Pharm. Des., 2007, vol. 13, pp. 463–470.

    Article  CAS  PubMed  Google Scholar 

  4. Freier, S.M. and Altmann, K.-H., Nucleic Acid Res., 1997, vol. 25, pp. 4429–4443.

    Article  CAS  PubMed  Google Scholar 

  5. Micklefield, J., Curr. Med. Chem., 2001, vol. 8, pp. 1157–1179.

    CAS  PubMed  Google Scholar 

  6. Kurreck, J., Eur. J. Biochem., 2003, vol. 270, pp. 1628–1644.

    Article  CAS  PubMed  Google Scholar 

  7. Tomohisa, M. and Kazuo, S., Frontiers in Organic Chemistry, 2005, vol. 1, pp. 163–194.

    Article  Google Scholar 

  8. Agrawal, S. and Zhao, Z., Curr. Opin. Chem. Biol., 1998, vol. 2, pp. 519–528.

    Article  CAS  PubMed  Google Scholar 

  9. Yu, D., Kandimalla, E.R., Roskey, A., Zhao, Q., Chen, L., Chen, J., and Agrawal, S., Bioorg. Med. Chem., 2005, vol. 8, pp. 275–284.

    Article  Google Scholar 

  10. Manoharan, M., Biochim. Biophys. Acta.-Gene Struct. Expres., 1999, vol. 1489, pp. 117–130.

    CAS  Google Scholar 

  11. Nielsen, P.E., Egholm, M., Berg, R.H., and Buchardt, O., Science, 1999, vol. 254, pp. 1497–1500.

    Article  Google Scholar 

  12. Larsen, H.J., Bentin, T., and Nielsen, P.E., Biochim. Biophys. Acta, 1999, vol. 1489, pp. 159–166.

    CAS  PubMed  Google Scholar 

  13. Koshkin, A.A., Singh, S.K., Nielsen, P., Rajwanshi, V.K., Kumar, R., Meldgaard, M., Olsen, C.E., and Wengel, J., Tetrahedron, 1988, vol. 54, pp. 3607–3630.

    Article  Google Scholar 

  14. Petersen, M., Bondensgaard, K., Wengel, J., and Jacobsen, J.P., J. Am. Chem. Soc., 2002, vol. 124, pp. 5974–5982.

    Article  CAS  PubMed  Google Scholar 

  15. Summerton, J., Stein, D., Huang, S.B., Matthews, P., Weller, S., and Partridge, M., Antisense Nucleic Acid Drug Dev., 1997, vol. 7, pp. 63–70.

    CAS  PubMed  Google Scholar 

  16. Summerton, J., Biochim. Biophys. Acta, 1999, vol. 1489, pp. 141–158.

    CAS  PubMed  Google Scholar 

  17. De Mesmaeker, A., Altmann, K.-H., Waldner, A., and Wendeborn, S., Curr. Opin. Struct. Biol., 1995, vol. 5, pp. 343–355.

    Article  PubMed  Google Scholar 

  18. Rozners, E., Current Organic Chem., 2006, vol. 10, pp. 675–692.

    Article  CAS  Google Scholar 

  19. Kochetkova, S.V., Varizhuk, A.M., Kolganova, N.A., Timofeev, E.N., and Florent’ev, V.L., Bioorg. Khim., 2009, vol. 35, pp. 202–209 [Russ. J. Bioorg. Chem. (Engl. Transl.), 2009, vol. 35, pp. 185–192].

    CAS  PubMed  Google Scholar 

  20. Varizhuk, A.M., Kochetkova, S.V., Kolganova, N.A., Timofeev, E.N., and Florent’ev, V.L., Bioorg. Khim., 2009, vol. 35 [Russ. J. Bioorg. Chem. (Engl. Transl.), 2009, vol. 35, pp. 650–656.

  21. Ogilvie, K.X, in Nucleosides, Nucleotides and Their Biological Applications, Rideout, J.L., Henry, D.W., and Beacham, L.M., Eds., New York: Academic, 1983, pp. 209–256.

    Google Scholar 

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Correspondence to V. L. Florent’ev.

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Original Russian Text © A.M. Varizhuk, S.V. Kochetkova, N.A. Kolganova, E.N. Timofeev, V.L. Florent’ev, 2010, published in Bioorganicheskaya Khimiya, 2010, Vol. 36, No. 2, pp. 215–222.

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Varizhuk, A.M., Kochetkova, S.V., Kolganova, N.A. et al. Oligonucleotide analogues containing a C3′-NH-C(O)-CH2-C5′ amide internucleotide bond. Russ J Bioorg Chem 36, 199–206 (2010). https://doi.org/10.1134/S1068162010020093

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  • DOI: https://doi.org/10.1134/S1068162010020093

Key words

  • oligonucleotides
  • analogues
  • amide internucleotide bond
  • hybridization
  • thermal stability