title: Sequence-dependent effects in drug-DNA interaction: the crystal structure of Hoechst 33258 bound to the d(CGCAAATTTGCG)2 duplex.
abstract: The bis-benzimidazole drug Hoechst 33258 has been co-crystallized with the dodecanucleotide sequence d(CGCAAATTTGCG)2. The structure has been solved by molecular replacement and refined to an R factor of 18.5% for 2125 reflections collected on a Xentronics area detector. The drug is bound in the minor groove, at the five base-pair site 5'-ATTTG and is in a unique orientation. This is displaced by one base pair in the 5' direction compared to previously-determined structures of this drug with the sequence d(CGCGAATTCGCG)2. Reasons for this difference in behaviour are discussed in terms of several sequence-dependent structural features of the DNA, with particular reference to differences in propeller twist and minor-groove width.
authors.affiliation: CRC Biomolecular Structure Unit, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: N
authors.initials: N
authors.lastname: Spink
authors.forename: D G
authors.initials: DG
authors.lastname: Brown
authors.forename: J V
authors.initials: JV
authors.lastname: Skelly
authors.forename: S
authors.initials: S
authors.lastname: Neidle
mesh_terms: D001483:Base Sequence; D006690:Bisbenzimidazole / Q000737:chemistry*; D003460:Crystallization; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry
chemical_list: D009838:Oligodeoxyribonucleotides; D004247:DNA; D006690:Bisbenzimidazole