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DNA Sequence-Specific Ligands. 19. Synthesis, Spectral Properties, Virological and Biochemical Studies of DB3(n) Fluorescent Dimeric Trisbenzimidazoles

  • STRUCTURAL AND FUNCTIONAL ANALYSIS OF BIOPOLYMERS AND THEIR COMPLEXES
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Abstract

In this work, we synthesized and characterized the properties of a series of new fluorescent DB3(n) narrow-groove ligands. DB3(n) compounds based on dimeric trisbenzimidazoles have the ability to bind to the AT regions of DNA. The synthesis of DB3(n), whose trisbenzimidazole fragments are linked by oligomethylene linkers of different lengths (n = 1, 5, 9), is based on the condensation of the MB3 monomeric trisbenzimidazole with α,ω-alkyldicarboxylic acids. DB3(n) proved to be effective inhibitors of the catalytic activity of HIV-1 integrase at submicromolar concentrations (0.20–0.30 µM). DB3(n) was found to inhibit the catalytic activity of DNA topoisomerase I at low micromolar concentrations.

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Funding

This work was supported by the Russian Foundation for Basic Research (no. 20-33-90287).

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    A. F. Arutyunyan, D. N. Kaluzhny & A. L. Zhuze

  2. Emanuel Institute of Biochemical Physics, Russian Academy of Science, 119334, Moscow, Russia

    A. A. Kostyukov

  3. Department of Chemistry, Moscow State University, 119991, Moscow, Russia

    S. P. Korolev & M. B. Gottikh

  4. Belozersky Institute of Physicochemical Biology, Moscow State University, 119991, Moscow, Russia

    S. P. Korolev & M. B. Gottikh

  5. Research Institute of Carcinogenesis, Blokhin National Medical Research Center of Oncology, 115478, Moscow, Russia

    O. Yu. Susova

Authors
  1. A. F. Arutyunyan
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  2. A. A. Kostyukov
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  3. S. P. Korolev
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  4. M. B. Gottikh
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  5. D. N. Kaluzhny
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  6. O. Yu. Susova
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  7. A. L. Zhuze
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Correspondence to A. L. Zhuze.

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The authors declare that they have no conflicts of interest. This article does not contain a description of studies performed by the authors involving humans or using animals as objects.

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Abbreviations: topo-I, DNA topoisomerase I; HIV-1, human immunodeficiency virus type 1; scDNA, supercoiled DNA; relaxDNA,relaxed DNA; PBS, phosphate buffered saline; IC50, 50% inhibitory concentration; HBTU, (2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; Boc-GlyOH, N-tert-butyloxycrbonylglycine; i-BuOC(O)Cl, isobutyl chloroformate; NMM, N-methylmorpholine; DMF, N,N-dimethylformamide; DIPEA, N,N-diisopropylethylamine.

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Arutyunyan, A.F., Kostyukov, A.A., Korolev, S.P. et al. DNA Sequence-Specific Ligands. 19. Synthesis, Spectral Properties, Virological and Biochemical Studies of DB3(n) Fluorescent Dimeric Trisbenzimidazoles. Mol Biol 57, 512–521 (2023). https://doi.org/10.1134/S0026893323030020

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