Click-Chemistry-Based Biomimetic Ligands Efficiently Capture G-Quadruplexes and Help Localize Them at DNA Damage Sites in Human Cells.
Fiche publication
Date publication
juillet 2022
Journal
JACS Au
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MONCHAUD David, Dr VALVERDE Ibai
Tous les auteurs :
Rota Sperti F, Dupouy B, Mitteaux J, Pipier A, Pirrotta M, Chéron N, Valverde IE, Monchaud D
Lien Pubmed
Résumé
Interrogating G-quadruplex (G4) biology at its deepest roots in human cells relies on the design, synthesis, and use of ever smarter molecular tools. Here, we demonstrate the versatility of biomimetic G4 ligands referred to as TASQ (template assembled synthetic G-quartet) in which a biotin handle was incorporated for G4-focused chemical biology investigations. We have rethought the biotinylated TASQ design to make it readily chemically accessible via an efficient click-chemistry-based strategy. The resulting biotinylated, triazole-assembled TASQ, or BioTriazoTASQ, was thus shown to efficiently isolate both DNA and RNA G4s from solution by affinity purification protocols, for identification purposes. Its versatility was then further demonstrated by optical imaging that provided unique mechanistic insights into the actual strategic relevance of G4-targeting strategies, showing that ligand-stabilized G4 sites colocalize with and, thus, are responsible for DNA damage foci in human cells.
Référence
JACS Au. 2022 07 25;2(7):1588-1595