Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Structure of TANDEM and its implication for bifunctional intercalation into DNA

Abstract

Quinoxaline antibiotics (Fig. 1a, b) form a useful group of compounds for the study of drug–nucleic acid interactions1,2. They consist of a cross-bridged cyclic octadepsipeptide, variously modified, bearing two quinoxaline chromophores. These antibiotics intercalate bifunctionally into DNA2,3 probably via the narrow groove, forming a complex in which, most probably, two base pairs are sandwiched between the chromophores4,5. Depending on the nature of their sulphur-containing cross-bridge and modifications to their amino acid side chains, they display characteristic patterns of nucleotide sequence selectivity when binding to DNAs of different base composition and to synthetic polydeoxynucleotides4,6,7. This specificity has been tentatively ascribed to specific hydrogen-bonding interactions between functional groups in the DNA and complementary moieties on the peptide ring2,4,5. Variations in selectivity have been attributed both to changes in the conformation of the peptide backbone6 and no modifications of the cross-bridge7. These suggestions were made, however, in the absence of firm knowledge about the three-dimensional structure and conformation of the antibiotic molecules. We now report the X-ray structure analysis of the synthetic analogue of the antibiotic triostin A, TANDEM (des-N-tetramethyl triostin A) (Fig. 1c), which binds preferentially to alternating adenine-thymine sequences7. The X-ray structure provides a starting point for exploring the origin of this specificity and suggests possible models for the binding of other members of the quinoxaline series.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. Katagiri, K., Yoshida, T. & Sato, K. in Antibiotics Vol. 3 (eds Corcoran, J. S. & Hahn, F. E.) 234–251 (Springer, Heidelberg, 1975).

    Google Scholar 

  2. Waring, M. J. in Antibiotics Vol. 5, Pt 2 (ed. Hahn, F. E.) 173–194 (Springer, Heidelberg, 1979).

    Google Scholar 

  3. Waring, M. J. & Wakelin, L. P. G. Nature 252, 653–657 (1974).

    ADS  CAS  Article  Google Scholar 

  4. Wakelin, L.P.G. & Waring, M. J. Biochem. J. 157, 721–740 (1976).

    CAS  Article  Google Scholar 

  5. Cheung, H. T. et al. J. Am. chem. Soc. 100, 46–54 (1978).

    CAS  Article  Google Scholar 

  6. Lee, J. S. & Waring, M. J. Biochem. J. 173, 115–128 (1978).

    CAS  Article  Google Scholar 

  7. Lee, J. S. & Waring, M. J. Biochem. J. 173, 129–144 (1978).

    CAS  Article  Google Scholar 

  8. Sheldrick, G. M. (in preparation).

  9. Fuller, W. & Waring, M. J. Ber. Bunsenges phys. Chem. 68, 805–808 (1964).

    CAS  Article  Google Scholar 

  10. Waring, M. J. in Drug Action at the Molecular Level (ed. Roberts, G. C. K.) 167–189 (Macmillan, London, 1977).

    Book  Google Scholar 

  11. Ughetto, G. & Waring, M. J. Molec. Pharmac. 13, 579–584 (1977).

    CAS  Google Scholar 

  12. Wang, J. C. J. molec. Biol. 89, 783–801 (1974).

    CAS  Article  Google Scholar 

  13. Kalman, J. R., Blake, T. J., Williams, D. H., Feeney, J. & Roberts, G. C. K. JCS Perkin I, 1313–1321 (1979).

    Article  Google Scholar 

  14. van der Helm, D. et al. (in preparation).

  15. Wang, A. H. J. et al. Nature 282, 680–686 (1979).

    ADS  CAS  Article  Google Scholar 

  16. Drew, H., Takano, T., Tanaka, S., Itakura, K. & Dickerson, R. E. Nature 286, 567–573 (1980).

    ADS  CAS  Article  Google Scholar 

  17. Levitt, M. Proc. natn. Acad. Sci. U.S.A. 75, 640–644 (1978).

    ADS  CAS  Article  Google Scholar 

  18. Hogan, M., Dattagupta, N. & Crothers, D. M. Proc. natn. Acad. Sci. U.S.A. 75, 195–199 (1978).

    ADS  CAS  Article  Google Scholar 

  19. Hogan, M., Dattagupta, N. & Crothers, D. M. Biochemistry 18, 280–288 (1979).

    CAS  Article  Google Scholar 

  20. Quigley, G. J. et al. Proc. natn. Acad. Sci. U.S.A. (in the press).

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Viswamitra, M., Kennard, O., Cruse, W. et al. Structure of TANDEM and its implication for bifunctional intercalation into DNA. Nature 289, 817–819 (1981). https://doi.org/10.1038/289817a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/289817a0

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing