title: Molecular recognition between ligands and nucleic acids: novel pyridine- and benzoxazole-containing agents related to Hoechst 33258 that exhibit altered DNA sequence specificity deduced from footprinting analysis and spectroscopic studies.
abstract: The syntheses of certain analogues of the DNA minor groove binding agent Hoechst 33258 designed to exhibit altered sequence recognition are described. The structural modifications include the following: substitution of pyridine for the benzene ring of the benzimidazole moiety, replacement of one benzimidazole unit by a benzoxazole in the two possible orientations with respect to the DNA receptor, and a synthesis of 2,2'-m-phenylene-bis[6-(4-methyl-1-piperazinyl)benzimidazole]. Sequence recognition of these agents on a HindIII/EcoRI fragment of pBR322 DNA was determined by MPE footprinting procedures. Some of the analogues exhibited altered DNA sequence preference compared with Hoechst 33258. In particular, a structure bearing a benzoxazole moiety with the oxygen oriented inward to the minor groove together with an inward-directed pyridine nitrogen appears to confer the property of recognition of a GC base pair within the binding sequence. The possible factors, structural, stereochemical, and electrostatic, contributing to the altered DNA sequence recognition properties are discussed.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Bathini
authors.forename: K E
authors.initials: KE
authors.lastname: Rao
authors.forename: R G
authors.initials: RG
authors.lastname: Shea
authors.forename: J W
authors.initials: JW
authors.lastname: Lown
mesh_terms: D001345:Autoradiography; D001483:Base Sequence; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000378:metabolism; D006690:Bisbenzimidazole / Q000031:analogs & derivatives*; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism; D004492:Edetic Acid / Q000031:analogs & derivatives; D008024:Ligands; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D001562:Benzimidazoles; D008024:Ligands; D009696:Nucleic Acids; C038200:methidiumpropyl-EDTA-iron(II); D004247:DNA; D004492:Edetic Acid; D006690:Bisbenzimidazole