Skip to main content
Log in

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

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hélène, C. & Toulmé, J.-J. Biochim. biophys. Acta 1049, 99–125 (1990).

    Article  Google Scholar 

  2. Goodchild, J. Bioconjugate Chem. 1, 165–187 (1990).

    Article  CAS  Google Scholar 

  3. Uhlmann, E. & Peyman, A. Chem. Rev. 90, 544–584 (1990).

    Article  Google Scholar 

  4. Eschenmoser, A. & Loewenthal, E. Chem. Soc. Rev. 21, 1–16 (1992).

    Article  CAS  Google Scholar 

  5. Nielsen, P. E., Egholm, M., Berg, R. H. & Buchardt, O. Science 254, 1497–1500 (1991).

    Article  ADS  CAS  Google Scholar 

  6. Egholm, M., Buchardt, O., Nielsen, P. E. & Berg, R. H. J. Am. Chem. Soc. 114, 1895–1897 (1992).

    Article  CAS  Google Scholar 

  7. Egholm, M., Buchardt, O., Nielsen, P. E. & Berg, R. H. J. Am. Chem. Soc. 114, 9677–9678 (1992).

    Article  CAS  Google Scholar 

  8. Egholm, M. et al. J. chem. Soc. chem. Commun. 800–801 (1993).

  9. Cherny, D. Y. et al. Proc. natn. Acad. Sci. U.S.A. 90, 1667–1670 (1993).

    Article  ADS  CAS  Google Scholar 

  10. Borer, P. N., Dengler, B., Tinoco, I. Jr. & Uhlenbeck, O. C. J. molec. Biol 86, 843–853 (1974).

    Article  CAS  Google Scholar 

  11. Freier, S. M., Burger, M. D., Alkema, D., Neilson, T. & Turner, D. Biochemistry 22, 6198–6206 (1983).

    Article  CAS  Google Scholar 

  12. Vesnaver, G. & Breslauer, K. J. Proc. natn. Acad. Sci. U.S.A. 88, 3569–3573 (1991).

    Article  ADS  CAS  Google Scholar 

  13. Orgel, L. Nature 358, 203–209 (1992).

    Article  ADS  CAS  Google Scholar 

  14. Cech, T. Proc. natn. Acad. Sci. U.S.A. 83, 4360–4364 (1986).

    Article  ADS  CAS  Google Scholar 

  15. Miller, S. L. Science 117, 528–529 (1953).

    Article  ADS  CAS  Google Scholar 

  16. Oro, J. Biochem. biophys. Res. Commun. 2, 407–415 (1960).

    Article  Google Scholar 

  17. Crook, S. T. Curr. Opinion. Biotech. 3, 656–661 (1992).

    Article  Google Scholar 

  18. Hanvey, J. C. et al. Science 258, 1481–1485 (1992).

    Article  ADS  CAS  Google Scholar 

  19. Nielsen, P. E., Egholm, M., Berg, R. H. & Buchardt, O. Anti-Cancer Drug Design 8, 53–63 (1993).

    CAS  PubMed  Google Scholar 

  20. Freier, S. M., Albergo, D. D. & Turner, D. Biopolymers 22, 1107 (1983).

    Article  CAS  Google Scholar 

  21. Maniatis, T., Fritsch, E. & Sambrook, J. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1982).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/365566a0

  • Springer Nature Limited

This article is cited by

Navigation