New oligodeoxynucleotide derivatives containing N-(o-nitrobenzenesulfonyl)-phosphoramide (nosyl phosphoramide), N-(1-butanesulfonyl)-phosphoramide (busyl phosphoramide), or N-(1-hexanesulfonyl)-phosphoramide groups are described. These compounds were first obtained via solid-phase synthesis on an automatic DNA synthesizer according to the Staudinger reaction between the corresponding sulfonylazides (nosyl, busyl or hesyl azides) and the oligonucleotide containing 3',5'-dinucleoside-β-cyanoethyl phosphide—phosphitamide condensation product—immobilized onto a polymer carrier. In this case, the rate of the Staudinger reaction on the solid phase is higher for more electrophilic nosyl azide than those of less electrophilic busyl and hesyl azides. The nosyl, busyl, and hesyl phosphoramide groups are stable under oligonucleotide synthesis conditions, including acid detritylation and removal of protective groups to form oligonucleotide from a polymer carrier via treatment with concentrated aqueous ammonia at 55°C. The oligonucleotides modified with either nosyl or busyl phosphoramide groups at all internucleotide positions were first prepared. We showed that the stability of complementary duplexes of oligodeoxynucleotides containing busyl or hesyl phosphoramide groups with a single-stranded DNA is insignificantly lower than that of a native DNA:DNA duplex, whereas the destabilization of the duplex is clearer for a bulky hesyl phosphoramide group. The oligonucleotides bearing busyl phosphoramide group form complementary duplexes with a complementary RNA being less stable than native DNA:RNA duplex, but more stable than similar heteroduplexes formed from RNA oligonucleotides and the tosyl phosphoramide group. These DNA N-(sulfonyl)-phosphoramide derivatives are considered to be potential antisense oligonucleotides.
This is a preview of subscription content, log in to check access.
Buy single article
Instant unlimited access to the full article PDF.
Price includes VAT for USA
Stephenson, M.L. and Zamecnik, P.C., Proc. Natl. Acad. Sci. U. S. A., 1978, vol. 75, pp. 285–288. https://doi.org/10.1073/pnas.75.1.285
Uhlmann, E. and Peyman, A., Chem. Rev., 1990, vol. 90, pp. 543–584. https://doi.org/10.1021/cr00102a001
De Mesmaeker, A., Haner, R., Martin, P., and Moser, H.E., Acc. Chem. Res., 1995, vol. 28, pp. 366–374. https://doi.org/10.1021/ar00057a002
Therapeutic Oligonucleotides, Goodchild, J., Ed., Methods Mol. Biol., Humana Press, 2011.
Sharma, V.K., Rungta, P., and Prasad, A.K., RSC Adv., 2014, vol. 4, pp. 16 618–16 631. https://doi.org/10.1039/c3ra47841f
Sharma, V.K., Sharma, R.K., and Singh, S.K., Med. Chem. Commun., 2014, vol. 5, pp. 1454–1471. https://doi.org/10.1039/c4md00184b
Miller, P.S., Agris, C.H., Aurelian, L., Blake, K.R., Murakami, A., Reddy, M.P., Spitz, S.A., and Ts’O, P.O., Biochimie, 1985, vol. 67, pp. 769–776. https://doi.org/10.1016/S0300-9084(85)80166-8
Eckstein, F., Antisense Nucleic Acids Drug Dev., 2009, vol. 10. pp. 117–121. https://doi.org/10.1089/oli.1.2000.10.117
Nielsen, J., Brill, W.K.D., and Caruthers, M.H., Tetrahedron Lett., 1988, vol. 29, pp. 2911–2914. https://doi.org/10.1016/0040-4039(88)85045-7
Rait, V.K. and Shaw, B.R., Antisense Nucleic Acid Drug Dev., 1999, vol. 9, pp. 53–60. https://doi.org/10.1089/oli.1.1999.9.53
Freier, S.M. and Altmann, K.-H., Nucleic Acids Res., 1997, vol.25, pp. 4429–4443. https://doi.org/10.1093/nar/25.22.4429
Beaucage, S.L. and Caruthers, M.H., 1981, vol. 22, pp. 1859–1862. https://doi.org/10.1016/S0040-4039(01)90461-7
Staudinger, H. and Meyer, J., Helv. Chim. Acta, 1919, vol. 2, pp. 635–646. https://doi.org/10.1002/hlca.19190020164
Kupryushkin, M.S., Apukhtina, V.S., Vasil’eva, S.V., Pyshnyi, D.V., and Stetsenko, D.A., Izv. Akad. Nauk,Ser. Khim., 2015, vol. 7, pp. 1678–1681.
Heindl, D., Kessler, D., Schube, A., Thuer, W., and Giraut, A., Nucleic Acids Symp. Ser., 2008, vol. 52, pp. 405–406. https://doi.org/10.1093/nass/nrn206
Heindl, D., F. Hoffman–La Roche Patent no. AG WO 2008/128686 A1, 2007.
Prokhorova, D.V., Chelobanov, B.P., Burakova, E.A., Fokina, A.A., and Stetsenko, D.A., Russ. J. Bioorg. Chem., 2017, vol. 43, no. 1, pp. 38–43.
Ruppel, J.V., Jones, J.E., Huff, C.A., Kamble, R.M., Chem, Y., and Zhang, P., Org. Lett., 2008, vol. 10, pp. 1995–1998. https://doi.org/10.1021/ol800588p
Matano, Y., Ohkubo, H., Honsho, Y., Saito, A., Seki, S., and Imahori, H., Org. Lett., 2013, vol. 15, pp. 932–935. https://doi.org/10.1021/ol4000982
Siewinski, M., Kuropatwa, M., and Szewczuk, A., Anal. Chem., 1984, vol. 56, pp. 2882–2884. https://doi.org/10.1021/ac00278a059
The authors are grateful to M. I. Meshchaninov (Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences) for his synthesis of 5'-r(UGUUUGGCGC) oligoribonucleotide.
This work was financially supported by the Russian Foundation for Basic Research (projects 18-29-09045, 18-515-57006, and 18-515-05007) and the Main Project “Therapeutic Nucleic Acids” for 2017–2020 (no. АААА-А17-117020210024-8).
COMPLIANCE WITH ETHICAL STANDARDS
This article does not contain any studies involving animals or human participants performed by any of the authors.
Conflict of Interest
There are no conflicts of interest to declare.
Translated by A. Tulyabaev
Abbreviations: DMTr, 4;4'-dimethoxytrityl; ESI, electrospray ionization; TEAA, triethylammonium acetate; Ns, nosyl-(o-nitrobenzene sulfonyl); RF HPLC, reverse phase high performance liquid chromatography; PAAG, polyacrylamide gel; all nucleotide sequences are 5'-3'; d prefix in the designations of oligodeoxynucleotides is omitted for clarity.
Corresponding author: phone: +7 (383) 363-51-51; fax: +7 (383) 363-51-53; e-mail: firstname.lastname@example.org.
About this article
Cite this article
Burakova, E.A., Derzhalova, A.S., Chelobanov, B.P. et al. New Oligodeoxynucleotide Derivatives Containing N-(Sulfonyl)-Phosphoramide Groups. Russ J Bioorg Chem 45, 662–668 (2019) doi:10.1134/S1068162019060098
- antisense oligonucleotides
- solid-phase synthesis
- Staudinger reaction
- sulfonyl azide