Modified Oligonucleotides for Guiding RNA Cleavage Using Bacterial RNase P

D. S. Novopashina, A. S. Nazarov, M. A. Vorobjeva, M. S. Kuprushkin, A. S. Davydova, A. A. Lomzov, D. V. Pyshnyi, S. Altman, A. G. Venyaminova

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Abstract

Abstract: The ability of a series of novel modified external guide sequences (EGS oligonucleotides) to induce the hydrolysis of target RNA with bacterial ribonuclease P has been studied; the most efficient modification variants have been selected. We have found patterns of the oligonucleotide sugar-phosphate backbone modi-fications that enhance oligonucleotide stability in the biological environment and do not violate the ability to interact with the enzyme and induce the RNA hydrolysis. It has been shown that analogues of EGS oligonucleotides selectively modified at 2'-position (2'-O-methyl and 2'-fluoro) or at internucleotide phosphates (phosphoryl guanidines) can be used for the addressed cleavage of a model RNA target by bacterial RNase P. The ability of new phosphoryl guanidine analogues of oligodeoxyribonucleotides that are stable in biological media to induce the hydrolysis of target RNA with bacterial ribonuclease P has been shown for the first time. The modified EGS oligonucleotides with an optimal balance between functional activity and stability in biological media can be considered as potential antibacterial agents.

Original languageEnglish
Pages (from-to)905-912
Number of pages8
JournalMolecular Biology
Volume52
Issue number6
DOIs
Publication statusPublished - 1 Nov 2018

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Keywords

  • 2'-fluoro modified oligoribonucleotides
  • bacterial RNase P
  • EGS oligonucleotides
  • modified oligonucleotides
  • oligo(2'-О-methylribonucleotides)
  • phosphoryl guanidine oligonucleotides
  • SEQUENCES
  • RIBONUCLEASE-P
  • PEPTIDE
  • NUCLEIC-ACIDS
  • INHIBITION
  • MORPHOLINO OLIGOMER CONJUGATE
  • RESISTANCE
  • oligo(2'-?-methylribonucleotides)
  • SUBUNIT

Cite this

Novopashina, D. S., Nazarov, A. S., Vorobjeva, M. A., Kuprushkin, M. S., Davydova, A. S., Lomzov, A. A., Pyshnyi, D. V., Altman, S., & Venyaminova, A. G. (2018). Modified Oligonucleotides for Guiding RNA Cleavage Using Bacterial RNase P. Molecular Biology, 52(6), 905-912. https://doi.org/10.1134/S0026893318060134