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Nucleic Acids Research, 1984, Vol. 12, No. 11 4679-4688
© 1984

CHEMISTRY

Binding of ethidium and bb(methidium)spermine to Z DNA by intercalation

Richard H. Shafer, Stephen C. Brown, Alain Delbarre* and Donald Wade

Department of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, CA 94143, USA

Received March 2, 1984. Revised May 15, 1984. Accepted May 15, 1984.

The interaction of ethidium bromide, a DNA intercalating drug, and bis(raethidium)spermine, a DNA bis-intercalating compound, with the left-handed Z form of poly(dG-dC) has been studied in 4.4 M NaCl. Spectrophotometric analysis using absorption, fluorescence and circular dichroism indicates that the complex formed between ethidium and Z DNA resembles very closely that formed with B DNA. This suggests that ethidium binds to Z DNA by intercalation. 31P NMR spectra are presented showing both the conversion of the Z form to the B form with increasing amounts of drug and the typical Z form spectrum at low binding densities. Data are also presented which show that the bifunctlonal intercalator bis(methidium)spermine binds to Z DNA in a manner similar to its binding to B DNA, i.e., by bis-interca-lation. These results are important for our understanding the behavior of Z DNA and its biological significance.

*Permanent address: Departernent de Chimie Organique, ERA613 (CNRS), SC 21 (INSERM), UER des Sciences Pharmaceutiques et Biologiques, 4 Avenue de PObservaloire, 75006 Paris, France


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