Photoactivatable, Biomimetic Ligand photoMultiTASQ Traps DNA/RNA G‑Quadruplexes and Their Protein Binding Partners.

Fiche publication

Date publication

décembre 2025

Journal

ACS bio & med chem Au

Auteurs

Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah , Dr MONCHAUD David , Dr VALVERDE Ibai

Tous les auteurs :
Raevens S, Danino YM, Desingle C, Rota Sperti F, Pirrotta M, Mazzucotelli L, Letissier L, Hornstein E, Cianferani S, Hernandez-Alba O, Valverde IE, Monchaud D

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/41425803

Résumé

The biological role of DNA and RNA G-quadruplexes (G4s) is relayed to the cellular circuitry by a plethora of proteins known as G4-binding proteins (G4PBs). It is thus critical to decipher the formation of the G4/G4BP complexes to accurately understand their involvement in G4-mediated regulatory mechanisms. While hundreds of G4-interacting compounds (G4 ligands) have been used to uncover G4 biology in a rather indirect manner, only a handful of multivalent ligands allowing for identifying associated proteins have been designed, mostly relying on the covalent capture of G4BPs upon photoactivation. We report herein on such a multivalent ligand named photoMultiTASQ, which belongs to a family of biomimetic and smart G4 ligands known as template-assembled synthetic G-quartets (TASQs). We show how photoMultiTASQ interacts with and photo-cross-links both DNA/RNA G4s and related G4BPs, and develop a new mass spectrometry (MS)-based technique to characterize the covalent adducts. Collectively, these results make photoMultiTASQ a new molecular tool in the arsenal of chemical cross-linking and isolation by pull-down (Chem-CLIP) technologies that uniquely identify targets and validate target engagement in cells.