Synthesis of oligonucleotides containing novel G-clamp analogue with C8-tethered group in phenoxazine ring: Implication to qPCR detection of the low-copy Kemerovo virus dsRNA

Anna M. Varizhuk, Timofei S. Zatsepin, Andrey V. Golovin, Evgeny S. Belyaev, Yury I. Kostyukevich, Vladimir G. Dedkov, German A. Shipulin, George V. Shpakovski, Andrey V. Aralov

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)

    Abstract

    Nowadays modified oligonucleotides are widely used in diagnostics and as novel therapeutics. Introduction of modified or unnatural residues into oligonucleotides allows fine tuning of their binding properties to complementary nucleic acids and leads to improved stability both in vitro and in vivo. Previously it was demonstrated that insertion of phenoxazine nucleotides with various groups in C9-position into oligonucleotides leads to a significant increase of duplex stability with complementary DNA and RNA. Here the synthesis of a novel G-clamp nucleoside analogue (G8AE-clamp) bearing 2-aminoethyl tether at C8-atom is presented. Introduction of such modified residues into oligonucleotides lead to enhanced specificity of duplex formation towards complementary DNA and RNA targets with increased thermal and 3′-exonuclease stability. According to CD-spectroscopy studies G8AE-clamp does not substantially disrupt helix geometry. Primers containing G8AE-clamp demonstrated superior sensitivity in qPCR detection of dsRNA of Kemerovo virus in comparison to native oligonucleotides.

    Original languageEnglish
    Pages (from-to)3597-3605
    Number of pages9
    JournalBioorganic and Medicinal Chemistry
    Volume25
    Issue number14
    DOIs
    Publication statusPublished - 2017

    Keywords

    • DNA mimics
    • G-clamp
    • Modification
    • Oligonucleotides
    • qPCR

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