Novel Bisimidazole-Containing Peptidomimetic Molecules for Мetal-Independent RNA Cleavage: Synthesis and Solid-Phase Screening Method
- Authors: Pavlova A.S.1, Ogurtsova P.A.1,2, Koroleva L.S.1, Serpokrylova I.Y.1, Lomzov A.A.1, Pyshnaya I.A.1, Silnikov V.N.1, Pyshnyi D.V.1,2
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Affiliations:
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
- Novosibirsk State University, Department of Natural Sciences
- Issue: Vol 45, No 6 (2019)
- Pages: 813-824
- Section: Article
- URL: https://journals.rcsi.science/1068-1620/article/view/229353
- DOI: https://doi.org/10.1134/S1068162019060311
- ID: 229353
Cite item
Abstract
Novel bisimidazole-containing peptidomimetic molecules, which can efficiently cleave RNA in the absence of divalent metal ions have been synthesized. The thymidine 5'-monophosphate derivatives modified with these peptidomimetics have been obtained on CPG (controlled pore glass) using a solid phase azide-alkyne cycloaddition. The ability of all synthesized derivatives to cleave RNA has been demonstrated by a solid-phase screening method. The resulting conjugates have provided a 20–100% cleavage of the RNA target in 18 hours. The results allow us to consider the described strategy as a useful approach for the rapid selection of potentially promising peptidomimetic molecules in order to synthesize reactive constructs on their basis.
About the authors
A. S. Pavlova
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: pyshnyi@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
P. A. Ogurtsova
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences; Novosibirsk State University, Department of Natural Sciences
Email: pyshnyi@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090; Novosibirsk,, 630090
L. S. Koroleva
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: pyshnyi@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
I. Y. Serpokrylova
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: pyshnyi@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
A. A. Lomzov
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: pyshnyi@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
I. A. Pyshnaya
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: pyshnyi@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
V. N. Silnikov
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: pyshnyi@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
D. V. Pyshnyi
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences; Novosibirsk State University, Department of Natural Sciences
Author for correspondence.
Email: pyshnyi@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090; Novosibirsk,, 630090
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