RNase P-Guiding Peptide Conjugates of Oligo(2'-O-methylribonucleotides) as Prospective Antibacterial Agents
- Authors: Danilin N.A.1, Koroleva L.S.1,2, Novopashina D.S.1,2, Venyaminova A.G.2
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Affiliations:
- Novosibirsk State University
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
- Issue: Vol 45, No 6 (2019)
- Pages: 825-832
- Section: Article
- URL: https://journals.rcsi.science/1068-1620/article/view/229360
- DOI: https://doi.org/10.1134/S106816201906013X
- ID: 229360
Cite item
Abstract
A novel variant of the synthesis of 3'- and 5'-peptide conjugates of oligo(2'-O-methylribonucleotides) has been developed using thiol-maleimide chemistry. The method is based on the introduction of the maleimide group into an oligonucleotide using a novel bifunctional reagent, pentafluorophenyl ester of 3‑maleimidopropionic acid (MPPf), and the subsequent interaction of the resulting compound with an SH‑bearing peptide, which facilitates cell penetration. A series of RNase P-guiding 3'- and 5'-peptide conjugates of oligo(2'-O-methylribonucleotides) targeted to mRNA of the ftsZ and gyrA genes of Acinetobacter baumannii have been synthesized. The ability of these conjugates to guide the hydrolysis of model RNA targets by RNase P has been demonstrated. It has been shown that the introduction of the peptide molecule at the 5'-end of EGS oligo(2'-O-methylribonucleotides) practically does not reduce the efficiency of RNA hydrolysis by RNAse P.
About the authors
N. A. Danilin
Novosibirsk State University
Email: danov@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
L. S. Koroleva
Novosibirsk State University; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: danov@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090; Novosibirsk, 630090
D. S. Novopashina
Novosibirsk State University; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Author for correspondence.
Email: danov@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090; Novosibirsk, 630090
A. G. Venyaminova
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: danov@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090