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

TITLE=Novel Peptide Conjugates of Modified Oligonucleotides for Inhibition of Bacterial RNase P

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00813

DOI=10.3389/fphar.2019.00813

ISSN=1663-9812

ABSTRACT=<p>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’-<italic>O</italic>-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 (<italic>Escherichia coli</italic> and <italic>Acinetobacter baumannii</italic>) and inhibit bacterial growth.</p>