DAUNOMYCIN INDUCES DEGLYCOSYLATION OF DNA: STRUCTURE OF d(CG[glucose-T]ACG)-DAUNOMYCIN COMPLEX. YiGui Gao, Howard Robinson, ⁺Jacques H. van Boom, Andrew H.-J. Wang, Biophysics Division & Dept. of Cell & Structural Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801 USA, ⁺Leiden Institute of Chemistry, Gorlaeus Laboratory, 2300 RA Leiden, The Netherlands

DNA from certain organisms contains unusually-modified DNA bases. For example, glycosylated-T or C at C5 position of the base is found in Trypanosoma Brucei. The role of those modified bases remains largely unknown, although in trypanosome they are believed to be involved in the regulation of gene expression. Ethidium bromide, an intercalator, has been shown to have an cytotoxic effect towards trypanosomes.

We have undertaken a structural study in which intercalator anticancer drug daunomycin was added to the modified DNA hexamer d(CG[glucose-T]ACG). The solution structure of the hexamer was determined by NMR. In addition, the three-dimensional molecular and crystal structure of the complex of daunomycin and the hexamer was determined at 1.7Å by X-ray diffraction analyses. Crystal data: P1, a = 18.63 Å, b = 20.01 Å, c = 26.54 Å, [[alpha]] = 69.30deg., [[beta]] = 90.31deg., [[gamma]] = 108.16deg., R=17.9%, 3385 reflections at 2[[sigma]]. Two daunomycin molecules bind to the DNA double helix. Unexpectedly we found that in the crystal structure one the glucose moieties is missing from the DNA. The biological implication of this will be addressed.

This work is supported by American Cancer Society DHP-114 to AHJW.