Skip to main content

Conjugates of RNase P-Guiding Oligonucleotides with Oligo(N-Methylpyrrole) as Prospective Antibacterial Agents

Abstract

The conjugates of RNase P guiding oligo(2'-O-methylribo)- and oligodeoxyribonucleotides (EGS oligonucleotides) with oligo(N-methylpyrrole) have been synthesized for the first time. The ability of RNase P to hydrolyze RNA in the presence of EGS oligonucleotides and their conjugates with oligo(N-methylpyrrole) has been demonstrated in model systems using fluorescently labeled chemically synthesized oligoribonucleotides corresponding to the fragments of mRNA of the ftsZ and gyrA genes of Acinetobacter baumannii. It has been shown that hydrolysis of RNA by RNase P occurs more efficiently in the presence of the conjugates than in the case of unmodified oligodeoxyribonucleotides. The introduction of oligo(N-methylpyrrole) in EGS oligo(2'-O-methylribonucleotides) insignificantly changes the effectiveness of hydrolysis. It has been demonstrated that the cell-penetrating ability of oligonucleotides is enhanced because of the presence of oligo(N-methylpyrrole) at the 5'-end.

This is a preview of subscription content, access via your institution.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.

REFERENCES

  1. Llor, C. and Bjerrum, L., Ther. Adv. Drug Saf., 2014, vol. 5, pp. 229–241. https://doi.org/10.1177/2042098614554919

    Article  PubMed  PubMed Central  Google Scholar 

  2. Guidry, C.A., Mansfield, S.A., Cook, C.H., and Sawyer, R.G., Surg. Clin. North Am., 2014, vol. 94, pp. 1195–1218. https://doi.org/10.1016/j.suc.2014.08.010

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bai, H., Xue, X., Hou, Z., Zhou, Y., Meng, J., and Luo, X., Curr. Drug Discov. Technol., 2010, vol. 7, pp. 76–85. https://doi.org/10.2174/157016310793180594

    CAS  Article  PubMed  Google Scholar 

  4. Walker, S.C. and Engelke, D.R., Crit. Rev. Biochem. Mol. Biol., 2006, vol. 41, pp. 77–102. https://doi.org/10.1080/10409230600602634

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. Forster, A.C. and Altman, S., Science, 1990, vol. 249, pp. 783–786. https://doi.org/10.1126/science.1697102

    CAS  Article  PubMed  Google Scholar 

  6. Davies-Sala, C., Soler-Bistué, A., Bonomo, R.A., Zorreguieta, A., and Tolmasky, M.E., Ann. N.Y. Acad. Sci., 2015, vol. 1354, pp. 98–110. https://doi.org/10.1111/nyas.12755

    CAS  Article  PubMed  Google Scholar 

  7. Derksen, M., Mertens, V., and Pruijn, G.J., Biomolecules, 2015, vol. 5, pp. 3029–3050. https://doi.org/10.3390/biom5043029

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Lundblad, E.W. and Altman, S., Nat. Biotechnol., 2010, vol. 27, pp. 212–221. https://doi.org/10.1016/j.nbt.2010.03.003

    CAS  Article  Google Scholar 

  9. Wesolowski, D., Tae, H.S., Gandotra, N., Llopis, P., Shen, N., and Altman, S., Proc. Natl. Acad. Sci. U. S. A., 2011, vol. 108, pp. 16582–16587. https://doi.org/10.1073/pnas.1112561108

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wesolowski, D., Alonso, D., and Altman, S., Proc. Natl. Acad. Sci. U. S. A., 2013, vol. 110, pp. 8686–8689. https://doi.org/10.1073/pnas.1306911110

    Article  PubMed  PubMed Central  Google Scholar 

  11. Soler, Bistué A.J.C., Martín, F.A., Vozza, N., Ha, H., Joaquín, J.C., Zorreguieta, A., and Tolmasky, M.E., Proc. Natl. Acad. Sci. U. S. A., 2009, vol. 106, pp. 13230–13235. https://doi.org/10.1073/pnas.0906529106

    Article  Google Scholar 

  12. Jackson, A., Jani, S., Sala, C.D., Soler-Bistué, A.J., Zorreguieta, A., and Tolmasky, M.E., Biol. Methods Protoc., 2016, vol. 1, p. bpw001. https://doi.org/10.1093/biomethods/bpw001

    Article  PubMed  PubMed Central  Google Scholar 

  13. Shen, N., Ko, J., Xiao, G., Wesolowski, D., Shan, G., Geller, B., Izadjoo, M., and Altman, S., Proc. Natl. Acad. Sci. U. S. A., 2009, vol. 106, pp. 8163–8168. https://doi.org/10.1073/pnas.0903491106

    Article  PubMed  PubMed Central  Google Scholar 

  14. Augagneur, Y., Wesolowski, D., Tae, H.S., Altman, S., and Ben Mamoun, C., Proc. Natl. Acad. Sci. U. S. A., 2012, vol. 109, pp. 6235–6240. https://doi.org/10.1073/pnas.1203516109

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sala, C.D., Soler-Bistué, A.J.C., Korprapun, L., Zorreguieta, A., and Tolmasky, M.E., PLoS One, 2012, vol. 7. e47690. https://doi.org/10.1371/journal.pone.0047690

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Sawyer, A.J., Wesolowski, D., Gandotra, N., Stojadinovic, A., Izadjoo, M., Altman, S., and Kyriakides, T.R., Int. J. Pharm., 2013, vol. 453, pp. 651–655. https://doi.org/10.1016/j.ijpharm.2013.05.041

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Danilin, N.A., Koroleva, L.S., Novopashina, D.S., and Venyaminova, A.G., Russ. J. Bioorg. Chem., 2019, vol. 45, pp. 825–832. https://doi.org/10.1134/S106816201906013X

    CAS  Article  Google Scholar 

  18. Jani, S., Jackson, A., Davies-Sala, C., Chiem, K., Soler-Bistué, A., Zorreguieta, A., and Tolmasky, M.E., Methods Mol. Biol., 2018, vol. 1737, pp. 89–98. https://doi.org/10.1007/978-1-4939-7634-8_6

    CAS  Article  PubMed  Google Scholar 

  19. Ahmad, A., Ranjan, S., Zhang, W., Zou, J., Pyykkö, I., and Kinnunen, P.K.J., Biochim. Biophys. Acta, 2015, vol. 1848, pp. 544–553. https://doi.org/10.1016/j.bbamem.2014.11.008

    CAS  Article  PubMed  Google Scholar 

  20. Kawamoto, Y., Bando, T., and Sugiyama, H., Bioorg. Med. Chem., 2018, vol. 26, pp. 1393–1411. https://doi.org/10.1016/j.bmc.2018.01.026

    CAS  Article  PubMed  Google Scholar 

  21. Lin, J. and Nagase, H., Biomolecules, 2020, vol. 10, p. 544. https://doi.org/10.3390/biom10040544

    CAS  Article  PubMed Central  Google Scholar 

  22. Dervan, P.B., Doss, R.M., and Marques, M.A., Curr. Med. Chem. Anti-Cancer Agents, 2005, vol. 5, pp. 373–387. https://doi.org/10.2174/1568011054222346

    CAS  Article  PubMed  Google Scholar 

  23. Wong, D., Nielsen, T.B., Bonomo, R.A., Pantapalangkoor, P., Luna, B., and Spellberg, B., Clin. Microbiol. Rev., 2017, vol. 30, pp. 409–447. https://doi.org/10.1128/CMR.00058-16

    CAS  Article  PubMed  Google Scholar 

  24. Harding, C.M., Hennon, S.W., and Feldman, M.F., Nat. Rev. Microbiol., 2018, vol. 16, pp. 91–102. https://doi.org/10.1038/nrmicro.2017.148

    CAS  Article  PubMed  Google Scholar 

  25. Doi, Y., Bonomo, R.A., Hooper, D.C., Kaye, K.S., Johnson, J.R., Clancy, C.J., Thaden, J.T., Stryjewski, M.E., and van Duin, D., Clin. Infect. Dis., 2017, vol. 64, suppl. 1, pp. S30–S35. https://doi.org/10.1093/cid/ciw829

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. Tacconelli, E., Carrara, E., Savoldi, A., Harbarth, S., Mendelson, M., Monnet, D.L., Pulcini, C., Kahlmeter, G., Kluytmans, J., Carmeli, Y., Ouellette, M., Outterson, K., Patel, J., Cavaleri, M., Mcox, E., Rhouchens, C.R., Grayson, L., Hansen, P., Singh, N., Theuretzbacher, U., Magrini, N., and the WHO Pathogens Priority List Working Group Aboderin, A.O., Al-Abri, S.S., Jalil, N.A., Benzonana, N., Bhattacharya, S., Brink, A.J., Burkert, F.R., Cars, O., Cornaglia, G., Dyar, O.J., Wfriedrich, A.W., Gales, A.C., Gandra, S., Giske, C.G., Goff, D.A., Goossens, H., Gottlieb, T., Blanco, M.G., Hryniewicz, W., Kattula, D., Jinks, T., Skanj, S.S., Kerr, L., Kieny, M.-P., Kim, Y.S., Kozlov, R.S., Labarca, J., Laxminarayan, R., Leder, K., Leibovici, L., Levy-Hara, G., Littman, J., Malhotra-Kumar, S., Manchanda, V., Moja, L., Ndoye, B., Pan, A., Paterson, D.L., Paul, M., Qiu, H., Ramon-Pardo, P., Rodríguez-Baño, J., Sanguinetti, M., Sengupta, S., Sharland, M., Si-Mehand, M., Lsilver, L.L., Song, W., Steinbakk, M., Thomsen, J., Thwaites, G.E., van der Meer, J.W.M., Kinh, N.V., Vega, S., Villegas, M.V., Wechsler-Fördös, A., Wertheim, H.F.L., Wesangula, E., Woodford, N., Oyilmaz, F.O., and Zorzet, A., Lancet. Infect. Dis., 2018, vol. 18, pp. 318–327. https://doi.org/10.1016/S1473-3099(17)30753-3

    Article  PubMed  Google Scholar 

  27. Tacconelli, E. and Magrini, N., Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics, Geneva: World Health Organization, 2018.

    Google Scholar 

  28. Vishnyakov, I.E. and Borchsenius, S.N., Cell Tissue Biol., 2007, vol. 1, pp. 206–214. https://doi.org/10.1134/S1990519X07030029

    Article  Google Scholar 

  29. Sidorenko, S.V. and Tishkov, V.I., Usp. Biol. Khim., 2004, vol. 44, pp. 263–306.

    CAS  Google Scholar 

  30. Cummins, L.L., Owens, S.R., Risen, L.M., Lesnik, E.A., Freier, S.M., McGee, D., Guinosso, C.J., and Cook, P.D., Nucleic Acids Res., 1995, vol. 23, pp. 2019–2024. https://doi.org/10.1093/nar/23.11.2019

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. Boutorine, A.S., Venyaminova, A.G., Repkova, M.N., Sergueyeva, Z.A., and Pyshnyi, D.V., Biochimie, 1994, vol. 76, pp. 23–32. https://doi.org/10.1016/0300-9084(94)90059-0

    CAS  Article  PubMed  Google Scholar 

  32. Novopashina, D.S., Nazarov, A.S., Vorobjeva, M.A., Kupryushkin, M.S., Davydova, A.S., Lomzov, A.A., Pyshnyi, D.V., Altman, S., and Venyaminova, A.G., Mol. Biol. (Moscow), 2018, vol. 52, pp. 905–912. https://doi.org/10.1134/S0026893318060134

    CAS  Article  Google Scholar 

  33. Jiang, X., Sunkara, N., Lu, S., and Liu, F., Methods Mol. Biol., 2014, vol. 1103, pp. 45–56. https://doi.org/10.1007/978-1-62703-730-3_4

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Perreault, J.P. and Altman, S., J. Mol. Biol., 1992, vol. 226, pp. 399–409. https://doi.org/10.1016/0022-2836(92)90955-j

    CAS  Article  PubMed  Google Scholar 

  35. Novopashina, D.S., Sinyakov, A.N., Ryabinin, V.A., Perrouault, L., Giovannangeli, C., Venyaminova, A.G., and Boutorine, A.S., Russ. J. Bioorg. Chem., 2013, vol. 39, pp. 138–152. https://doi.org/10.1134/S1068162013010081

    CAS  Article  Google Scholar 

  36. Guerrier-Takada, C., Lumelsky, N., and Altman, S., Science, 1989, vol. 246, pp. 1578–1584. https://doi.org/10.1126/science.2480641

    CAS  Article  PubMed  Google Scholar 

  37. Guerrier-Takada, C., Gardiner, K., Marsh, T., Pace, N., and Altman, S., Cell, 1983, vol. 35, pp. 849–857. https://doi.org/10.1016/0092-8674(83)90117-4

    CAS  Article  PubMed  Google Scholar 

Download references

ACKNOWLEDGMENTS

The authors would like to thank Prof. Sidney Altman for the initiation of the work concerning EGS technologies in our Institute, Dr. Donna Wesolowski for kindly providing plasmids to prepare the components of RNase P holoenzyme; Dr. V.A. Ryabinin and Dr. A.N. Sinyakov for the synthesis and isolation of oligo-(N-methylpyrrole); Dr. A.A. Chernonosov for recording the mass spectra, Dr. N.A. Moor and Dr. S.N. Khodyreva for the preparation and isolation of RNA M1 and C5 protein, respectively.

Funding

The work was supported by the State-funded budget projects (Program of fundamental scientific research of the State Academies of Sciences for 2013-2020 [АААА-А17-117020210021-7]).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. S. Novopashina.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

This article does not contain any studies with the use of humans as objects of research.

Conflict of Interests

The authors state that there is no conflict of interest.

Additional information

Translated by A. Levina

Abbreviations: EGS, external guide sequence; Flu, the fluorescein residue; L1, oligo(N-methylpyrrole).

Corresponding author: phone: +7 (383) 363-51-29; fax: +7 (383) 363-51-53.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Danilin, N.A., Matveev, A.L., Tikunova, N.V. et al. Conjugates of RNase P-Guiding Oligonucleotides with Oligo(N-Methylpyrrole) as Prospective Antibacterial Agents. Russ J Bioorg Chem 47, 469–477 (2021). https://doi.org/10.1134/S1068162021020084

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162021020084

Keywords:

  • oligo(2'-O-methylribonucleotides)
  • bacterial RNAse P
  • EGS-oligonucleotides
  • oligo(N-methylpyrrole)