Novel peptide conjugates of modified oligonucleotides for inhibition of bacterial RNase P

Darya Novopashina, Mariya Vorobyeva, Anton Nazarov, Anna Davydova, Nikolay Danilin, Lyudmila Koroleva, Andrey Matveev, Alevtina Bardasheva, Nina Tikunova, Maxim Kupryushkin, Dmitrii Pyshnyi, Sidney Altman, Alya Venyaminova

Research output: Contribution to journalArticle

Abstract

Novel alternatives to traditional antibiotics are now of great demand for the successful treatment of microbial infections. Here, we present the engineering and properties of new oligonucleotide inhibitors of RNase P, an essential bacterial enzyme. The series of 2’-O-methyl RNA (2’-OMe-RNA) and phosphoryl guanidine oligonucleotides were targeted to the substrate-binding region of M1 RNA subunit of the RNase P. Uniformly modified 2’-OMe RNA and selectively modified phosphoryl guanidine oligonucleotides possessed good stability in biological media and effectively inhibited RNase P. Their conjugates with transporting peptides were shown to penetrate bacterial cells (Escherichia coli and Acinetobacter baumannii) and inhibit bacterial growth.

Original languageEnglish (US)
Article number813
JournalFrontiers in Pharmacology
Volume10
DOIs
StatePublished - Jul 2019

Keywords

  • Antibacterial activity
  • Bacterial RNase P
  • Inhibition of RNase P
  • Modified oligonucleotides
  • Oligo(2’-O-methylribonucleotides)
  • Penetration into bacterial cells
  • Peptide conjugates of oligonucleotides
  • Phosphoryl guanidine oligonucleotides

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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  • Cite this

    Novopashina, D., Vorobyeva, M., Nazarov, A., Davydova, A., Danilin, N., Koroleva, L., Matveev, A., Bardasheva, A., Tikunova, N., Kupryushkin, M., Pyshnyi, D., Altman, S., & Venyaminova, A. (2019). Novel peptide conjugates of modified oligonucleotides for inhibition of bacterial RNase P. Frontiers in Pharmacology, 10, [813]. https://doi.org/10.3389/fphar.2019.00813