A MACROCYCLIC BIS-ACRIDINE SHIFTS THE EQUILIBRIUM FROM DUPLEXES TOWARDS DNA HAIRPINS

Nucleic acids can undergo dynamic conformational changes associated wi th the regulation of biological processes, A molecule presenting large r affinities for alternative structures relative to a duplex is expect ed to modify such conformational equilibria, We have previously report ed that macrocyclic bis-acridine binds preferentially to single-strand ed regions, especially DNA hairpins, due to steric effects, Here, we s how, using gel electrophoresis, fluorescence and melting temperature e xperiments, that the macrocycle bis-acridine shifts an equilibrium fro m 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 extr apolation, the macrocycle bis-acridine should be able to disrupt, at l east locally, genomic DNA duplexes and to stabilize unpaired areas, es pecially palindromic ones forming hairpins, Such macrocyclic compounds may have potential applications in the therapy of diseases involving hairpins.