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Vol 52(2018) N 6 p. 905-912; DOI 10.1134/S0026893318060134 Full Text

D.S. Novopashina1,2*, A.S. Nazarov1,2, M.A. Vorobjeva1, M.S. Kuprushkin1, A.S. Davydova1, A.A. Lomzov1,2, D.V. Pyshnyi1,2, S. Altman3,4, A.G. Venyaminova1

Modified Oligonucleotides for Guiding RNA Cleavage Using Bacterial RNase P

1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russia
2Novosibirsk State University, Novosibirsk, 630090 Russia
3Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520 USA
4Division of Life Sciences, Arizona State University, Tempe, AZ, USA

*danov@niboch.nsc.ru
Received - 2017-12-28; Accepted - 2018-04-06

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.

bacterial RNase P, EGS oligonucleotides, modified oligonucleotides, oligo(2'-О-methylribonucleotides), 2'-fluoro modified oligoribonucleotides, phosphoryl guanidine oligonucleotides



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