Journal
FRONTIERS IN PHARMACOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2019.00813
Keywords
bacterial RNase P; inhibition of RNase P; modified oligonucleotides; oligo(2 '-O-methylribonucleotides); phosphoryl guanidine oligonucleotides; peptide conjugates of oligonucleotides; penetration into bacterial cells; antibacterial activity
Categories
Funding
- RFBR [17-04-01892]
- Russian State-funded budget project of ICBFM SB RAS [AAAA-A17-117020210021-7]
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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 baumannir) and inhibit bacterial growth.
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