A Cationic Tetraphenylethene as a Light-Up Supramolecular Probe for DNA G-Quadruplexes

Clément Kotras (1, 2) , Mathieu Fossépré (3) , Maxime Roger (1) , Virginie Gervais (4) , Sebastien Richeter (1) , Philippe Gerbier (1) , Sébastien Ulrich (5) , Mathieu Surin (3) , Sébastien Clément (1)

1 ICGM - Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier
2 Laboratory for Chemistry of Novel Materials
3 Laboratory for Chemistry of Novel Materials
4 IPBS - Institut de pharmacologie et de biologie structurale
5 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

Guanine-quadruplexes (G4s) are targets for anticancer therapeutics. In this context, human telomeric DNA (HT-DNA) that can fold into G4s sequences are of particular interest, and their stabilization with small molecules through a visualizable process has become a challenge. As a new type of ligand for HT-G4, we designed a tetraimidazolium tetraphenylethene (TPE-Im) as a water-soluble light-up G4 probe. We study its G4-binding properties with HT-DNA by UV-Visible absorption, circular dichroism and fluorescence spectroscopies, which provide insights into the interactions between TPE-Im and G4-DNA. Remarkably, TPE-Im shows a strong fluorescence enhancement and large shifts upon binding to G4, which is valuable for detecting G4s. The association constants for the TPE-Im/G4 complex were evaluated in different solution conditions via isothermal titration calorimetry (ITC), and its binding modes were explored by molecular modeling showing a groove-binding mechanism. The stabilization of G4 by TPE-Im has been assessed by Fluorescence Resonance Energy Transfer (FRET) melting assays, which show a strong stabilization (1T1/2 around +20◦C), together with a specificity toward G4 with respect to double-stranded DNA.

Mots clés: fluorescence; G-quadruplexes; tetraphenylethene; light-up probe; supramolecular

Domaines: Chimie

Clément Kotras, Mathieu Fossépré, Maxime Roger, Virginie Gervais, Sebastien Richeter, et al.. A Cationic Tetraphenylethene as a Light-Up Supramolecular Probe for DNA G-Quadruplexes. Frontiers in Chemistry, 2019, 7, ⟨10.3389/fchem.2019.00493⟩. ⟨hal-02183007⟩