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A Comparative Study of the Hybridization of Phosphoryl Guanidine Oligonucleotides with DNA and RNA

Abstract—

The structure and thermal stability of complexes of RNA and DNA with phosphoryl guanidine oligonucleotides (PGO) bearing modified phosphate residues in which 1,3-dimethylimidazolidin-2-imine residues are introduced at the phosphorus atom have been studied. The substitution of the negatively charged oxygen atom in the structure of the internucleoside phosphate residue of an oligodeoxyribonucleotide by an electroneutral tetraalkyl-substituted guanidine residue does not lead to significant changes in the conformation of the PGO/RNA duplex compared to the native DNA/RNA complex. Their secondary structure is typical for the A-form of the double helix of hybrid complexes and differs from that of the RNA/RNA duplex. The introduction of modifications leads to a decrease in the thermal stability of PGO/RNA complexes under standard conditions (1.01 М Na+, neutral рН values). The magnitude of destabilization weakly depends on the nucleotide context in which the modification is located; on average, the thermal stability decreases by 1.2°С per one modified phosphate residue. The duplexes of fully substituted PGO with DNA have thermal stability that does not depend on the concentration of cations in solution. In contrast, the case of PGO/RNA complex, a significant decrease (by ~6°С) in thermal stability on changes from standard conditions to deionized water (Milli-Q) is observed. For comparison, the thermal stability of native duplexes on changes in buffer conditions decreases by more than 40°С. The changes in the thermal stability associated with the introduction of modifications are due to changes both in the enthalpy and entropy of complex formation.

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REFERENCES

  1. Chernikov, I.V., Vlassov, V.V., and Chernolovskaya, E.L., Front. Pharmacol., 2019, vol. 10, p. 444. https://doi.org/10.3389/fphar.2019.00444

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Shen, W., De Hoyos, C.L., Migawa, M.T., Vickers, T.A., Sun, H., Low, A., and Bell, M., Nat. Biotechnol., 2019, vol. 37, pp. 640–650. https://doi.org/10.1038/s41587-019-0106-2

    CAS  Article  PubMed  Google Scholar 

  3. Benizri, S., Gissot, A., Martin, A., Vialet, B., Grinstaff, M.W., and Barthelemy, P., Bioconjugate Chem., 2019, vol. 30, pp. 366–383. https://doi.org/10.1021/acs.bioconjchem.8b00761

    CAS  Article  Google Scholar 

  4. Kupryushkin, M.S., Pyshnyi, D.V., and Stetsenko, D.A., Acta Naturae, 2014, vol. 6, pp. 123–125.

    Article  Google Scholar 

  5. Stetsenko, D.A., WO Patent no. WO2016028187A1, 2016.

  6. Kuznetsov, N.A., Kupryushkin, M.S., Abramova, T.V., Kuznetsova, A.A., Miroshnikova, A.D., Stetsenko, D.A., Pyshnyi, D.V., and Fedorova, O.S., Mol. BioSyst., 2016, vol. 12, pp. 67–75. https://doi.org/10.1039/C5MB00692A

    CAS  Article  PubMed  Google Scholar 

  7. Lebedeva, N.A., Anarbaev, R.O., Kupryushkin, M.S., Rechkunova, N.I., Pyshnyi, D.V., Stetsenko, D.A., and Lavrik, O.I., Bioconjugate Chem., 2015, vol. 26, pp. 2046–2053. https://doi.org/10.1021/acs.bioconjchem.5b00451

    CAS  Article  Google Scholar 

  8. Garafutdinov, R.R., Sakhabutdinova, A.R., Kupryushkin, M.S., and Pyshnyi, D.V., Biochimie, 2020, vol. 168, pp. 259–267. https://doi.org/10.1016/j.biochi.2019.11.013

    CAS  Article  PubMed  Google Scholar 

  9. Dmitrienko, E., Naumova, O., Fomin, B., Kupryushkin, M., Volkova, A., Amirkhanov, N., Semenov, D., Pyshnaya, I., and Pyshnyi, D., Nanomedicine, 2016, vol. 11, pp. 2073–2082. https://doi.org/10.2217/nnm-2016-0071

    CAS  Article  PubMed  Google Scholar 

  10. Epanchintseva, A., Dolodoev, A., Grigor’eva, A., Chelobanov, B., Pyshnyi, D., Ryabchikova, E., and Pyshnaya, I., Nanotecnology, 2018, vol. 29, p. 355601. https://doi.org/10.1088/1361-6528/aac933

    CAS  Article  Google Scholar 

  11. Markov, A.V., Kupryushkin, M.S., Goncharova, E.P., Amirkhanov, R.N., Vasilyeva, S.V., Pyshnyi, D.V., Zenkova, M.A., and Logashenko, E.B., Russ. J. Bioorg. Chem., 2019, vol. 45, pp. 774–782.

    CAS  Article  Google Scholar 

  12. Dyudeeva, E.S., Kupryushkin, M.S., Lomzov, A.A., Pyshnaya, I.A., and Pyshnyi, D.V., Russ. J. Bioorg. Chem., 2019, vol. 45, pp. 709–718. https://doi.org/10.1134/S1068162019060153

    CAS  Article  Google Scholar 

  13. Lomzov, A.A., Golyshev, V.M., Dyudeeva, E.S., Kupryushkin, M.S., and Pyshnyi, D.V., J. Biomol. Struct. Dynam., 2019, vol. 37, pp. 83–84. https://doi.org/10.1080/07391102.2019.1604468

    Article  Google Scholar 

  14. Ivanov, V.I., Minchenkova, L.E., Schyolkina, A.K., and Poletayev, A.I., Biopolymers, 1973, vol. 12, pp. 89–110. https://doi.org/10.1002/bip.1973.360120109

    CAS  Article  PubMed  Google Scholar 

  15. Kypr, J., Kejnovská, I., Ren\(\check{c}\)iuk, D., and Vorli\(\check{c}\)ková, M., Nucleic Acids Res., 2009, vol. 37, pp. 1713–1725. https://doi.org/10.1093/nar/gkp026

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Lomzov, A.A., Kupryushkin, M.S., Shernyukov, A.V., Nekrasov, M.D., Dovydenko, I.S., Stetsenko, D.A., and Pyshnyi, D.V., Biochem. Biophys. Res. Commun., 2019, vol. 513, pp. 807–811. https://doi.org/10.1016/j.bbrc.2019.04.024

    CAS  Article  PubMed  Google Scholar 

  17. Searle, M.S. and Williams, D.H., Nucleic Acids Res., 1993, vol. 21, pp. 2051–2056. https://doi.org/10.1093/nar/21.9.2051

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. Vargas-Lara, F., Starr, F.W., and Douglas, J.F., Soft Matter, 2017, vol. 13, pp. 8309–8330. https://doi.org/10.1039/C7SM01220A

    CAS  Article  PubMed  Google Scholar 

  19. Tataurov, A.V., You, Y., and Owczarzy, R., Biophys. Chem., 2008, vol. 133, pp. 66–70. https://doi.org/10.1016/j.bpc.2007.12.004

    CAS  Article  PubMed  Google Scholar 

  20. Lokhov, S.G. and Pyshnyi, D.V., FEBS Lett., 1998, vol. 420, pp. 134–138. https://doi.org/10.1016/S0014-5793(97)01502-0

    Article  Google Scholar 

  21. Marky, L.A. and Breslauer, K.J., Biopolymers, 1987, vol. 26, pp. 1601–1620. https://doi.org/10.1002/bip.360260911

    CAS  Article  PubMed  Google Scholar 

  22. Schroeder, S.J. and Turner, D.H., Methods Enzymol., 2009, vol. 468, pp. 371–387. https://doi.org/10.1016/S0076-6879(09)68017-4

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Lomzov, A.A. and Pyshnyi, D.V., Biophysics (Oxford), 2012, vol. 57, pp. 19–34. https://doi.org/10.1134/S0006350912010137

    CAS  Article  Google Scholar 

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ACKNOWLEDGMENTS

The authors would like to thank LLC Noogen for the synthesis and provision of phosphoryl guanidine oligonucleotides and M.I. Meshchaninova for the synthesis and isolation of oligonucleotides.

Funding

The analysis of the structures and thermal stability of PGO complexes was carried out with the support of the Russian Science Foundation (project no. 18-14-00357).

The isolation of oligonucleotides was performed by the methods developed previously within the framework of the basic budgetary funding (project A-0309-2016-0004).

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Correspondence to A. A. Lomzov or D. V. Pyshnyi.

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COMPLIANCE WITH ETHICAL STANDARDS

The paper does not contain any studies involving animal or human participants performed by any of the authors.

Conflict of Interests

M.S. Kupryushkin and D.V. Pyshnyi are the cofounders of LLC Noogen, which is the copyright holder of phosphoryl guanidine oligonucleotides and the method of their synthesis.

A.A. Lomzov and E.S. Dyudeeva declare that they have no conflict of interest.

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Translated by S. Sidorova

Abbreviations: DMI, N,N,N',N-substituted guanidine residue (1,3-dimethylimidazolidin-2-imine); ESI, electrospray ionization; BLM, bilayer lipid membrane; PG, phosphoryl guanidine; PGO, phosphoryl guanidine oligonucleotides.

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Lomzov, A.A., Kupryushkin, M.S., Dyudeeva, E.S. et al. A Comparative Study of the Hybridization of Phosphoryl Guanidine Oligonucleotides with DNA and RNA. Russ J Bioorg Chem 47, 461–468 (2021). https://doi.org/10.1134/S1068162021020151

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  • DOI: https://doi.org/10.1134/S1068162021020151

Keywords:

  • nucleic acid analogs
  • modified oligonucleotides
  • phosphoryl guanidine oligonucleotides
  • thermal stability
  • duplex