title: A macrocyclic bis-acridine shifts the equilibrium from duplexes towards DNA hairpins.
abstract: Nucleic acids can undergo dynamic conformational changes associated with the regulation of biological processes. A molecule presenting larger affinities for alternative structures relative to a duplex is expected to modify such conformational equilibria. We have previously reported that macrocyclic bis-acridine binds preferentially to single-stranded regions, especially DNA hairpins, due to steric effects. Here, we show, using gel electrophoresis, fluorescence and melting temperature experiments, that the macrocycle bis-acridine shifts an equilibrium from a duplex towards the corresponding hairpins. Competition experiments enlighten the higher affinity of the macrocycle for hairpins compared with double-stranded DNA. The macrocycle bis-acridine destabilizes a synthetic polynucleotide, by the formation of premelted areas. By extrapolation, the macrocycle bis-acridine should be able to disrupt, at least locally, genomic DNA duplexes and to stabilize unpaired areas, especially palindromic ones forming hairpins. Such macrocyclic compounds may have potential applications in the therapy of diseases involving hairpins.
authors.affiliation: Laboratoire de Spectroscopie Biomoléculaire, URA CNRS 1430, UFR de Santé, Médecine et Biologie Humaine, Université Paris XIII, Bobigny, France. schwok@ibpc.fr
authors.forename: A
authors.initials: A
authors.lastname: Slama-Schwok
authors.forename: F
authors.initials: F
authors.lastname: Peronnet
authors.forename: E
authors.initials: E
authors.lastname: Hantz-Brachet
authors.forename: E
authors.initials: E
authors.lastname: Taillandier
authors.forename: M P
authors.initials: MP
authors.lastname: Teulade-Fichou
authors.forename: J P
authors.initials: JP
authors.lastname: Vigneron
authors.forename: M
authors.initials: M
authors.lastname: Best-Belpomme
authors.forename: J M
authors.initials: JM
authors.lastname: Lehn
mesh_terms: D000166:Acridines / Q000494:pharmacology*; D001667:Binding, Competitive; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D046911:Macromolecular Substances; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009994:Osmolar Concentration; D011067:Poly dA-dT / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D000166:Acridines; D004277:DNA, Single-Stranded; D046911:Macromolecular Substances; C106828:macrocyclic bis-acridine; D011067:Poly dA-dT; D004247:DNA