TY - JOUR
T1 - Novel peptide conjugates of modified oligonucleotides for inhibition of bacterial RNase P
AU - Novopashina, Darya
AU - Vorobyeva, Mariya
AU - Nazarov, Anton
AU - Davydova, Anna
AU - Danilin, Nikolay
AU - Koroleva, Lyudmila
AU - Matveev, Andrey
AU - Bardasheva, Alevtina
AU - Tikunova, Nina
AU - Kupryushkin, Maxim
AU - Pyshnyi, Dmitrii
AU - Altman, Sidney
AU - Venyaminova, Alya
N1 - Funding Information:
The research was carried out with financial support by the RFBR grant N 17-04-01892. In the part of the synthesis of modified oligonucleotides, the work was supported by the Russian State-funded budget project of ICBFM SB RAS # АААА-А17-117020210021-7.
Publisher Copyright:
© 2019 Novopashina, Vorobyeva, Nazarov, Davydova, Danilin, Koroleva, Matveev, Bardasheva, Tikunova, Kupryushkin, Pyshnyi, Altman and Venyaminova.
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
KW - Antibacterial activity
KW - Bacterial RNase P
KW - Inhibition of RNase P
KW - Modified oligonucleotides
KW - Oligo(2’-O-methylribonucleotides)
KW - Penetration into bacterial cells
KW - Peptide conjugates of oligonucleotides
KW - Phosphoryl guanidine oligonucleotides
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U2 - 10.3389/fphar.2019.00813
DO - 10.3389/fphar.2019.00813
M3 - Article
AN - SCOPUS:85083969058
SN - 1663-9812
VL - 10
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 813
ER -