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PNA hybridizes to complementary oligonucleotides obeying the Watson–Crick hydrogen-bonding rules

Nature volume 365, pages 566–568 (1993)Cite this article

Abstract

DNA ANALOGUES are currently being intensely investigated owing to their potential as gene-targeted drugs1–3. Furthermore, their properties and interaction with DNA and RNA could provide a better understanding of the structural features of natural DNA that determine its unique chemical, biological and genetic properties3,4. We recently designed a DNA analogue, PNA, in which the backbone is structurally homomorphous with the deoxyribose backbone and consists of N-(2-aminoethyl)glycine units to which the nucleobases are attached5–9. We showed that PNA oligomers containing solely thymine and cytosine can hybridize to complementary oligonucleotides, presumably by forming Watson–Crick–Hoogsteen (PNA)2–DNA triplexes, which are much more stable than the corresponding DNA–DNA duplexes5–7, and bind to double-stranded DNA by strand displacement5,8. We report here that PNA containing all four natural nucleobases hybridizes to complementary oligonucleotides obeying the Watson–Crick base-pairing rules, and thus is a true DNA mimic in terms of base-pair recognition.

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Authors and Affiliations

  1. Department of Organic Chemistry, The H. C. Ørsted Institute, Universitetsparken 5, DK-2100 Ø, Copenhagen, Denmark

    Michael Egholm, Ole Buchardt, Leif Christensen & Carsten Behrens

  2. ISIS Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, California, 82008, USA

    Susan M. Freier & David A. Driver

  3. Polymer Group, Materials Department, Risø National Laboratory, DK, 4000, Roskilde, Denmark

    Rolf H. Berg

  4. Department of Physical Chemistry, Chalmers University of Technology, S-41296, Gothenburg, Sweden

    Seog K. Kim & Bengt Norden

  5. Research Center for Medical Biotechnology, Department of Biochemistry B, The Panum Institute, Blegdamsvej 3c, 2200, Copenhagen N, Denmark

    Peter E. Nielsen

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  1. Michael Egholm
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Egholm, M., Buchardt, O., Christensen, L. et al. PNA hybridizes to complementary oligonucleotides obeying the Watson–Crick hydrogen-bonding rules. Nature 365, 566–568 (1993). https://doi.org/10.1038/365566a0

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