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

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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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

Keywords:

  • modified oligonucleotides
  • phosphoryl guanidines
  • mass spectrometry
  • anchimeric effect