title: Design and synthesis of heterocyclic cations for specific DNA recognition: from AT-rich to mixed-base-pair DNA sequences.
abstract: The compounds synthesized in this research were designed with the goal of establishing a new paradigm for mixed-base-pair DNA sequence-specific recognition. The design scheme starts with a cell-permeable heterocyclic cation that binds to AT base pair sites in the DNA minor groove. Modifications were introduced in the original compound to include an H-bond accepting group to specifically recognize the G-NH that projects into the minor groove. Therefore, a series of heterocyclic cations substituted with an azabenzimidazole ring has been designed and synthesized for mixed-base-pair DNA recognition. The most successful compound, 12a, had an azabenzimidazole to recognize G and additional modifications for general minor groove interactions. It binds to the DNA site -AAAGTTT- more strongly than the -AAATTT- site without GC and indicates the design success. Structural modifications of 12a generally weakened binding. The interactions of the new compound with a variety of DNA sequences with and without GC base pairs were evaluated by thermal melting analysis, circular dichroism, fluorescence emission spectroscopy, surface plasmon resonance, and molecular modeling.
authors.affiliation: Department of Chemistry, Georgia State University , Atlanta, Georgia 30303, United States.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chai
authors.forename: Ananya
authors.initials: A
authors.lastname: Paul
authors.forename: Michael
authors.initials: M
authors.lastname: Rettig
authors.forename: W David
authors.initials: WD
authors.lastname: Wilson
authors.forename: David W
authors.initials: DW
authors.lastname: Boykin
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D002412:Cations / Q000737:chemistry*; D002942:Circular Dichroism; D004247:DNA / Q000138:chemical synthesis* / Q000737:chemistry*; D019281:Dimerization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D013050:Spectrometry, Fluorescence; D020349:Surface Plasmon Resonance / Q000379:methods
chemical_list: D002412:Cations; D006571:Heterocyclic Compounds; D004247:DNA