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Nucleic Acids Research, 1992, Vol. 20, No. 10 2411-2420
© 1992

CHEMISTRY

Proton NMR study of the [d(ACGTATACGT)]2-2echinomycin complex: conformational changes between echinomycin binding sites

Dara E. Gilbert+ and Juli Feigon*

Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California at Los Angeles Los Angeles, CA 90024, USA

* To whom correspondence should be addressed

Received April 18, 1992. Accepted April 21, 1992.

The interactions of echinomycin and the DNA decamer [d(ACGTATACGT)]2 were studied by proton NMR. Echinomycin binds cooperatively as a bisintercalator at the CpG steps. The terminal A·T base pairs are Hoogsteen base paired, but none of the four central A·T base pairs are Hoogsteen base paired. However, binding of the drug induces unwinding of the DNA which is propagated to the central ApT step. All four central A·T base pairs are destabilized relative to those in the free DNA. Furthermore, based on these and other results from our laboratory, we conclude that the formation of stable Hoogsteen base pairs may not be the relevant structural change in vivo. The structural changes propagated between adjacent ACGT binding sites are the unwinding of the duplex and destabilization of the base pairing between binding sites.

+ Present address: Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, NL-3584 CH, Utrecht, The Netherlands


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