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Synthesis of Novel Representatives of Phosphoryl Guanidine Oligonucleotides

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Abstract

Novel representatives of phosphoryl guanidine oligonucleotide derivatives were prepared in this study. A synthetic scheme has been proposed and implemented suitable for the preparation of a wide range of diaminocarbenium azides starting from various secondary amines for subsequent incorporation of tetrasubstituted guanidine residues into the oligonucleotides by the Staudinger reaction. A number of factors which affected the yield of the phosphoryl guanidine derivative were identified, in particular, the size of the alkyl substituents in the azide used, the purity of the azide, and the conditions for elimination of the protecting cyanoethyl group before the final deprotection of the oligonucleotide.

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ACKNOWLEDGMENTS

We would like to thank the Joint Center for Collective Use of the Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, for the mass spectroscopic analysis of the oligonucleotides and A.S. Chubarov (junior research worker of the Biomedical Chemistry Laboratory of the Institute of Chemical Biology and Fundamental Medicine) for recording the NMR spectra.

Funding

This study was supported by the base budgetary financing of the Program of the Basic Scientific Research of the State Scientific Academies in 2013–2020, projects nos. АААА-А17-117020210024-8. M.S. Kupryushkin thanks the Russian Scientific Foundation (project no. 19-14-00204) for the support of the synthesis and characterization of the native and modified oligonucleotides.

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Authors and Affiliations

  1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    S. A. Zhukov, D. V. Pyshnyi & M. S. Kupryushkin

  2. Novosibirsk State University, 630090, Novosibirsk, Russia

    D. V. Pyshnyi

Authors
  1. S. A. Zhukov
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  2. D. V. Pyshnyi
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  3. M. S. Kupryushkin
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Corresponding author

Correspondence to M. S. Kupryushkin.

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COMPLIANCE WITH ETHICAL STANDARDS

This article does not contain any studies involving human participants and animals performed by any of the authors.

Conflict of Interests

M.S. Kupryushkin and D.V. Pyshnyi are cofounders of OOO NooGen. This company develops the technology for the preparation of phosphoryl guanidine oligonucleotides and their application. S.A. Zhukov declares that he has no conflicts of interest.

Additional information

Translated by L. Onoprienko

Abbreviations: ADMP, hexafluorophosphate of 2-azido-1,3-dimethylimidazolinium; CPG, controlled-pore glass; DIPEA, N,N-diisopropylethylamine; NA, nucleic acid; rpHPLC, reversed-phase high performance liquid chromatography.

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Zhukov, S.A., Pyshnyi, D.V. & Kupryushkin, M.S. Synthesis of Novel Representatives of Phosphoryl Guanidine Oligonucleotides. Russ J Bioorg Chem 47, 380–389 (2021). https://doi.org/10.1134/S1068162021020291

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