title: Probing A-form DNA: A fluorescent aminosugar probe and dual recognition by anthraquinone-neomycin conjugates.
abstract: Nucleic acids adopt a broad array of hydrogen-bonded structures that enable their diverse roles in the cell; even the familiar DNA double helix displays subtle architectural nuances that are sequence dependent. While there have been many approaches for recognition of B-form nucleic acids, A-form DNA recognition has lagged behind. Here, using a tight binding fluorescein-neomycin (F-neo) conjugate that can probe the electrostatic environment of A-form DNA major groove, we developed a fluorescent displacement assay to be used as a screen for DNA duplex-binding compounds. As opposed to intercalating dyes that can significantly perturb DNA structure, the groove binding F-neo allows the probing of native DNA conformation. In combination with the assay development and probing of DNA grooves, we also report the synthesis and binding of a series of neomycin-anthraquinone conjugates, two units with a known preference for binding GC rich DNA. The assay can be used to identify duplex DNA-binding compounds, as well as probe structural features of a target DNA duplex, and can easily be scaled up for high throughput screening of compound libraries.
authors.affiliation: NUBAD, LLC, Greenville, SC 29607, USA.
authors.forename: Derrick
authors.initials: D
authors.lastname: Watkins
authors.affiliation: Department of Chemistry, Clemson University, Clemson, SC 29634, USA.
authors.forename: Changjun
authors.initials: C
authors.lastname: Gong
authors.affiliation: Department of Chemistry, Clemson University, Clemson, SC 29634, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kellish
authors.affiliation: NUBAD, LLC, Greenville, SC 29607, USA; Department of Chemistry, Clemson University, Clemson, SC 29634, USA. Electronic address: dparya@clemson.edu.
authors.forename: Dev P
authors.initials: DP
authors.lastname: Arya
mesh_terms: D044704:DNA, A-Form / Q000032:analysis*; D019793:Fluorescein / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000032:analysis*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009355:Neomycin / Q000737:chemistry*
chemical_list: D044704:DNA, A-Form; D005456:Fluorescent Dyes; D009355:Neomycin; D019793:Fluorescein
keywords: DNA; DNA biophysics; DNA groove; Drug-DNA interactions