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

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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.

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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]).

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Authors and Affiliations

  1. Novosibirsk State University, 630090, Novosibirsk, Russia

    N. A. Danilin & D. S. Novopashina

  2. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    N. A. Danilin, A. L. Matveev, N. V. Tikunova, A. G. Venyaminova & D. S. Novopashina

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  1. N. A. Danilin
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  2. A. L. Matveev
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  3. N. V. Tikunova
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Correspondence to D. S. Novopashina.

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

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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.

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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

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