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Highly Efficient Site-Directed RNA Cleavage by Imidazole-Containing Conjugates of Antisense Oligonucleotides

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Abstract

A method has been suggested for the synthesis of conjugates of oligodeoxyribonucleotides with chemical constructs mimicking the ribonuclease A active center for directed fragmentation of RNA. The method is based on sequential addition of a linker group, 9-(methylamino)anthracene, to the 5"- or 3"-terminal phosphate of oligonucleotide, and then an imidazole-containing construct by cycloaddition. The conjugates of oligonucleotides complementary to regions 44–61 (2B–R) and 60–76 (1C–R) of yeast phenylalanine tRNA proved able to cleave tRNAPhe under physiological conditions preferentially at the sole phosphodiester bond (C63–A64 for 2B–R and C56–G57 for 1C–R, respectively). The half-time of tRNAPhe hydrolysis in the presence of 2B–R conjugate was 30 min at a 2B–R concentration of 10 μM and several minutes at conjugate concentration of 50 μM.

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Authors and Affiliations

  1. Institute of Bioorganic Chemistry, Siberian Division, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    N. G. Beloglazova, A. Yu. Epanchintsev, V. N. Sil'nikov, M. A. Zenkova & V. V. Vlasov

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  1. N. G. Beloglazova
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  2. A. Yu. Epanchintsev
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  3. V. N. Sil'nikov
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  4. M. A. Zenkova
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  5. V. V. Vlasov
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Beloglazova, N.G., Epanchintsev, A.Y., Sil'nikov, V.N. et al. Highly Efficient Site-Directed RNA Cleavage by Imidazole-Containing Conjugates of Antisense Oligonucleotides. Molecular Biology 36, 581–588 (2002). https://doi.org/10.1023/A:1019821707065

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