Identification of trinucleotide repeat ligands with a FRET melting assay.
DNA hairpin structures formed within a repeated tract might be a causative factor for triplet expansion observed in several debilitating diseases. We have designed and used a fluorescence resonance energy transfer (FRET) melting assay to screen for ligands that bind specifically to the CNG triplet repeats. Using this assay, we screened a panel of 33 chemicals that were previously designed to bind DNA or RNA secondary structures. Remarkably, we found that macrocyclic compounds, such as acridine dimers and trimers, exhibit interesting affinities and specificities for this motif.
Amrane
Samir
S
Muséum National d'Histoire Naturelle (MNHN) USM 503, INSERM U565, CNRS UMR 5153, Case Postale 26, 57 rue Cuvier 75005 Paris, France.
De Cian
Anne
A
Rosu
Frédéric
F
Kaiser
Markus
M
De Pauw
Edwin
E
Teulade-Fichou
Marie-Paule
MP
Mergny
Jean-Louis
JL
D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D008024:Ligands; D044366:Transition Temperature; D018911:Trinucleotide Repeats
D008024:Ligands