title: Comparative study of affinity and selectivity of ligands targeting abasic and mismatch sites in DNA using a fluorescence-melting assay.
abstract: Recently, several families of small-molecule ligands have been developed to selectively target DNA pairing defects, such as abasic sites and mismatched base pairs, with the aim to interfere with the DNA repair and the template function of the DNA. However, the affinity and selectivity (with respect to well-matched DNA) of these ligands has barely been evaluated in a systematic way. Herein, we report a comparative study of binding affinity and selectivity of a representative panel of 16 ligands targeting abasic sites and a T-T mismatch in DNA, using a fluorescence-monitored melting assay. We demonstrate that bisintercalator-type macrocyclic ligands are characterized by moderate affinity but exceptionally high selectivity with respect to well-matched DNA, whereas other reported ligands show either modest selectivity or rather low affinity in identical conditions.
authors: Institut Curie, PSL Research University, CNRS UMR9187, INSERM U1196, F-91405, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR9187, INSERM U1196, F-91405, Orsay, France.
authors: Naoko
authors: N
authors: Kotera
authors: Institut Curie, PSL Research University, CNRS UMR9187, INSERM U1196, F-91405, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR9187, INSERM U1196, F-91405, Orsay, France. Electronic address: anton.granzhan@curie.fr.
authors: Anton
authors: A
authors: Granzhan
authors: Institut Curie, PSL Research University, CNRS UMR9187, INSERM U1196, F-91405, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR9187, INSERM U1196, F-91405, Orsay, France.
authors: Marie-Paule
authors: MP
authors: Teulade-Fichou
mesh_terms: D020137:Base Pair Mismatch / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D005453:Fluorescence; D008024:Ligands; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D044366:Transition Temperature
chemical_list: D008024:Ligands; D004247:DNA
keywords: Abasic site; DNA ligands; DNA recognition; FRET melting assay; Thermal denaturation