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


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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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.


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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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.

Corresponding author: phone: +7 (383) 363-51-35.

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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).

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