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Problems of the Synthesis of Oligonucleotide Derivatives in the Realization of the Anchimeric Effect

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Abstract

It has been found that the presence of a free OH group at the 3'-terminal residue of the substituted ethylene glycol fragment in a phosphoryl guanidine oligodeoxyribonucleotide derivative is a factor that determines the instability of the structure of the target oligonucleotide product under the conditions of a standard deblocking protocol. It has been shown that the main by-products of the realization of the anchimeric effect of the OH group are the products of the transesterification of the phosphoryl guanidine (PG) unit carrying the O-substituted ethylene glycol residue. The data of the mass spectrometry analysis indicate that, under alkaline conditions, the accumulation of derivatives devoid of the N,N,N',N'-substituted guanidine residue (1,3-dimethylimidazolidin-2-imine, DMI) or the entire 3'-terminal PG-containing nonnucleotide unit occurs.

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Funding

The work on the analysis and implementation of the anchimeric effect was supported by the Russian Foundation for Basic Research (project no. 19-34-90132) and is a continuation of pilot studies on mass spectrometry analysis supported by the Russian Science Foundation in 2019 (project no. 18-14-00357).

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Authors and Affiliations

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

    E. S. Dyudeeva, A. S. Pavlova, M. S. Kupryushkin, D. V. Pyshnyi & I. A. Pyshnaya

  2. Novosibirsk State Research University, 630090, Novosibirsk, Russia

    D. V. Pyshnyi

Authors
  1. E. S. Dyudeeva
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  2. A. S. Pavlova
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  3. M. S. Kupryushkin
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  4. D. V. Pyshnyi
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  5. I. A. Pyshnaya
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Corresponding author

Correspondence to I. A. Pyshnaya.

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The paper does not contain any studies involving animal or human participants performed by any of the authors.

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The authors declare that there is no conflict of interest.

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Translated by S. Sidorova

Abbreviations: CPG, controlled-pore glass; DMI, 1,3-dimethylimidazolidin-2-imine, the N,N,N',N'-substituted guanidine residue; ESI MS, electrospray ionization mass spectrometry; NA, nucleic acid; the prefix d (deoxyribo-) is omitted (unless otherwise indicated); ON, oligonucleotide; RPC, reversed-phase chromatography; PG, phosphoryl guanidine unit; PGO, phosphoryl guanidine oligodeoxyribonucleotide.

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Dyudeeva, E.S., Pavlova, A.S., Kupryushkin, M.S. et al. Problems of the Synthesis of Oligonucleotide Derivatives in the Realization of the Anchimeric Effect. Russ J Bioorg Chem 47, 505–513 (2021). https://doi.org/10.1134/S1068162021020096

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  • DOI: https://doi.org/10.1134/S1068162021020096

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