title: Efficient inhibition of human AP endonuclease 1 (APE1) via substrate masking by abasic site-binding macrocyclic ligands.
abstract: Bis-naphthalene macrocycles, which bind with high affinity and selectivity to abasic sites in DNA, efficiently inhibit their cleavage by APE1 (IC50 = 55-60 nM in the kinetic assay with a model THF substrate). These results demonstrate that substrate masking by non-covalent abasic-site ligands is an efficient strategy for inhibition of APE1.
authors.affiliation: CNRS UMR9187/INSERM U1196 "Chemistry, Modelling and Imaging for Biology", Centre de Recherche, Institut Curie, 91405 Orsay, France. anton.granzhan@curie.fr.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kotera
authors.forename: Florent
authors.initials: F
authors.lastname: Poyer
authors.forename: Anton
authors.initials: A
authors.lastname: Granzhan
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
mesh_terms: D000818:Animals; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D002417:Cattle; D004247:DNA / Q000737:chemistry; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004996:Ethidium / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007364:Intercalating Agents / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D047028:Macrocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D009281:Naphthalenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C503406:7-nitro-1H-indole-2-carboxylic acid; D004791:Enzyme Inhibitors; D007211:Indoles; D007364:Intercalating Agents; D008024:Ligands; D047028:Macrocyclic Compounds; D009281:Naphthalenes; D001312:Aurintricarboxylic Acid; D004247:DNA; C427203:calf thymus DNA; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004996:Ethidium