Identification of trinucleotide repeat ligands with a FRET melting assay
Samir Amrane1, Anne De Cian, Frédéric Rosu
1Muséum National d'Histoire Naturelle (MNHN) USM 503, INSERM U565, CNRS UMR 5153, Case Postale 26, 57 rue Cuvier 75005 Paris, France.
Abstract:
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.
