Novel Bisimidazole-Containing Peptidomimetic Molecules for Мetal-Independent RNA Cleavage: Synthesis and Solid-Phase Screening Method


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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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