title: Mixed up minor groove binders: Convincing A·T specific compounds to recognize a G·C base pair.
abstract: DNA minor-groove-binding compounds have limited biological applications, in part due to problems with sequence specificity that cause off-target effects. A model to enhance specificity has been developed with the goal of preparing compounds that bind to two AT sites separated by G·C base pairs. Compounds of interest were probed using thermal melting, circular dichroism, mass spectrometry, biosensor-SPR, and molecular modeling methods. A new minor groove binder that can strongly and specifically recognize a single G·C base pair with flanking AT sequences has been prepared. This multi-site DNA recognition mode offers novel design principles to recognize entirely new DNA motifs.
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Ananya
authors.initials: A
authors.lastname: Paul
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Rupesh
authors.initials: R
authors.lastname: Nanjunda
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Arvind
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Laughlin
authors.affiliation: UMR-S1172-Jean-Pierre Aubert Research Centre (JPARC), INSERM-University of Lille and Centre Hospitalier of Lille, Institut pour la Recherche sur le Cancer de Lille, Place de Verdun, F-59045 Lille Cedex, France.
authors.forename: Raja
authors.initials: R
authors.lastname: Nhili
authors.affiliation: UMR-S1172-Jean-Pierre Aubert Research Centre (JPARC), INSERM-University of Lille and Centre Hospitalier of Lille, Institut pour la Recherche sur le Cancer de Lille, Place de Verdun, F-59045 Lille Cedex, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Depauw
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Shelby Sheldon
authors.initials: SS
authors.lastname: Deuser
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Arpana S
authors.initials: AS
authors.lastname: Chaudhary
authors.affiliation: UMR-S1172-Jean-Pierre Aubert Research Centre (JPARC), INSERM-University of Lille and Centre Hospitalier of Lille, Institut pour la Recherche sur le Cancer de Lille, Place de Verdun, F-59045 Lille Cedex, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: David-Cordonnier
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Boykin
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA. Electronic address: wdw@gsu.edu.
authors.forename: W David
authors.initials: WD
authors.lastname: Wilson
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D001555:Benzene Derivatives / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D062105:Molecular Docking Simulation; D015394:Molecular Structure
chemical_list: D001555:Benzene Derivatives; D004247:DNA
keywords: Biophysical analysis; Heterocyclic diamidines; Mixed DNA recognition; Rational design; Sequence specificity