Interrogating G-quadruplex (G4) biology at its deepest roots in human cells relies on the design, synthesis, and use of ever smarter molecular tools.
In this article, we designed a biomimetic G4 ligand referred to as BioTriazoTASQ in which a biotin handle was incorporated. BioTriazoTASQ was used as a molecular bait for fishing G4s by affinity purification protocols. Its versatility was then further demonstrated by optical imaging that provided unique mechanistic insights into the actual strategic relevance of G4-targetting strategies, showing that ligand-stabilized G4 sites colocalize with and, thus, are responsible for DNA damage foci in human cells.
Now published in JACS Au: Click chemistry-based biomimetic ligands efficiently capture G-quadruplexes in vitro and help localize them at DNA damage sites in human cells. Francesco Rota Sperti, Baptiste Dupouy, Jérémie Mitteaux, Angélique Pipier, Marc Pirrotta, Nicolas Chéron, Ibai E. Valverde and David Monchaud, JACS Au, 2, 1588, https://doi.org/10.1021/jacsau.2c00082.