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Synthesis of a new intercalating nucleic acid analogue with pyrenol insertions and the thermal stability of the resulting oligonucleotides towards DNA over RNA

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Abstract

A new intercalating nucleic acid monomer Y was obtained via alkylation of pyren-1-ol with (S)-(+)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol under Mitsunobu conditions followed by hydrolysis with 80% aqueous acetic acid to give a diol which was tritylated with 4,4′-dimethoxytrityl chloride followed by treatment with 2-cyanoethyltetraisopropylphosphordiamidite in the presence of N,N′-diisopropylammonium tetrazolide. In this way the monomer Y was obtained as its dimethoxytrityl-protected phosphoramidite building block for standard DNA synthesis. The corresponding oligonucleotides from Y have nearly identical hybridization properties with those of intercalating nucleic acid (INA) where neighboring oxygen and carbon atoms are interchanged in the linker. The synthesis of monomer Y avoids the use of allergic intermediates which are a problem in the synthesis of INA.

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Acknowledgments

This work was supported by the Sixth Framework Program Marie Curie Host Fellowships for Early Stage Research Training under contract number MEST-CT-2004-504018 and by the Nucleic Acid Center, which is funded by The Danish National Research Foundation for studies on nucleic acid chemical biology.

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Authors and Affiliations

  1. Department of Physics and Chemistry, Nucleic Acid Center, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark

    Amany M. A. Osman & Erik B. Pedersen

  2. Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koam, Egypt

    Amany M. A. Osman

Authors
  1. Amany M. A. Osman
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  2. Erik B. Pedersen
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Correspondence to Erik B. Pedersen.

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The Nucleic Acid Center is a research center funded by The Danish National Research Foundation for studies on nucleic acid chemical biology.

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Osman, A.M.A., Pedersen, E.B. Synthesis of a new intercalating nucleic acid analogue with pyrenol insertions and the thermal stability of the resulting oligonucleotides towards DNA over RNA. Monatsh Chem 141, 817–822 (2010). https://doi.org/10.1007/s00706-010-0320-6

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  • DOI: https://doi.org/10.1007/s00706-010-0320-6

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