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1.
Nucleic Acids Res ; 25(13): 2574-81, 1997 Jul 01.
Article in English | MEDLINE | ID: mdl-9185566

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.


Subject(s)
Acridines/pharmacology , DNA/chemistry , Nucleic Acid Conformation/drug effects , Binding, Competitive , DNA/metabolism , DNA, Single-Stranded/metabolism , Electrophoresis, Agar Gel , Macromolecular Substances , Osmolar Concentration , Poly dA-dT/chemistry , Poly dA-dT/metabolism , Spectrometry, Fluorescence
2.
Chem Phys Lipids ; 63(3): 169-77, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1493613

ABSTRACT

We have investigated the effect on phospholipidic bilayers of LEW-10, a synthetic flavonoid, derivative of diosmin. Two optical techniques, Quasi-elastic Light Scattering (QLS) and Fourier Transform Infrared Spectroscopy (FT-IR) were used. The results show that in the presence of LEW-10, the phase transition of the bilayers is lowered and that the elastic modulus is decreased. The FT-IR results indicate interactions in the aqueous interface regions of the bilayers. We also discuss LEW-10 comparatively with another derivative, LEW-7/S1, whose effect has been previously studied.


Subject(s)
Diosmin/analogs & derivatives , Lipid Bilayers , Phospholipids , Carbohydrate Sequence , Elasticity , Fourier Analysis , Hot Temperature , Light , Molecular Sequence Data , Molecular Structure , Scattering, Radiation , Spectrophotometry, Infrared
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