DNA-Binding by analogs of the left-half of azinomycin: A minimal DNA-intercalating structure

TOXI 55

Joseph Szekely, jozsef.szekely@vanderbilt.edu, Deartment of Biochemistry, Vanderbilt University, 7330 Stevenson Center, Station B Box 1822, Nashville, TN 37235, Hong Zang, hz136@mizzou.edu, Department of Chemistry, University of Missouri-Columbia, 601 South College Avenue, Columbia, MO 65211, Michael Shipman, m.shipman@warwick.ac.uk, Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, United Kingdom, and Kent S. Gates, GatesK@missouri.edu, Departments of Chemistry and Biochemistry, University of Missouri - Columbia, 601 S. College Ave., Columbia, MO 65211.
Previous work from our group established that the naphthalene ring found in azinomycin confers noncovalent DNA-binding properties on this antitumor natural product, but the mode of DNA association (intercalation or groove binding?) has remained controversial. In the work reported here, we used synthetic analogues of azinomycin to characterize the environment of the napthalene ring in covalent azinomycin-guanine adducts in duplex DNA. Plasmid winding assays, fluorescence contact energy transfer (FCET) assays and, ultimately, viscosity studies indicate that the naphthalene ring of the azinomycin analogues examined here is intercalated into duplex DNA in the covalent complex.

 

Poster Session and Awards
6:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- 204 A/B, Poster

Division of Chemical Toxicology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007