Fiche publication
Date publication
avril 2019
Journal
Journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DELMAS Dominique
,
Dr MONCHAUD David
Tous les auteurs :
Duskova K, Lamarche J, Amor S, Caron C, Queyriaux N, Gaschard M, Penouilh MJ, De Robillard G, Delmas D, Devillers CH, Granzhan A, Teulade-Fichou MP, Chavarot-Kerlidou M, Therrien B, Britton S, Monchaud D
Lien Pubmed
Résumé
The human genome is replete with repetitive DNA sequences that can fold into thermodynamically stable secondary structures such as hairpins and quadruplexes. Cellular enzymes exist to cope with these structures whose stable accumulation would result in DNA damage through interference with DNA transactions such as transcription and replication. Therefore, chemical stabilization of secondary DNA structures offers an attractive way to foster DNA transaction-associated damages to trigger cell death in proliferating cancer cells. While much emphasis has been recently given to DNA quadruplexes, we focused here on three-way DNA junctions (TWJ) and report on a strategy to identify TWJ-targeting agents through a combination of in vitro techniques (TWJ-Screen, PAGE, FRET-melting, ESI-MS, dialysis equilibrium and SRB assays). We designed a complete workflow and screened 1200 compounds to identify promising TWJ-ligands selected on stringent criteria in terms of TWJ folding ability, affinity and selectivity.
Référence
J. Med. Chem.. 2019 Apr 3;:
