Three‐dimensional crystal structure of the A‐tract DNA dodecamer d(CGCAAATTTGCG) complexed with the minor‐groove‐binding drug Hoechst 33258

Open Access
Publisher Website
Google Scholar
Abstract
The molecular structure of the DNA A‐tract dodecamer d(CGCAAATTTGCG) complexed with the drug Hoechst 33258 has been determined by X‐ray diffraction analysis. The Hoechst molecule binds in the DNA minor groove covering the sequence AATTT of the central A‐tract, with the piperazine group close to one of the GC regions. The drug molecule makes two three‐centered hydrogen bonds from the nitrogen atoms of the benzimidazole rings to the N3 and O2 atoms of the DNA bases. Although a high propeller twist is observed in the A‐tract, only one unsymmetrical three‐centered hydrogen bond is present in the DNA major groove. The structure is compared with other minor‐groove‐binding drug complexes and the influence of these drugs on DNA A‐tracts is discussed.