G-Quadruplex binding optimization by gold( iii ) insertion into the center of a porphyrin

Angélique Pipier (1) , Aurore de Rache (2) , Coralie Modeste (1) , Samir Amrane (2) , Emmanuelle Mothes-Martin (3) , Jean-Luc Stigliani (3) , Patrick Calsou (1) , Jean-Louis Mergny (2, 4) , Geneviève Pratviel (3) , Dennis Gomez (1)

1 IPBS - Institut de pharmacologie et de biologie structurale
2 ARNA - Acides Nucléiques : Régulations Naturelle et Artificielle
3 LCC - Laboratoire de chimie de coordination
4 Institute of Biophysics ASCR [Brno, Czech Republic]

Porphyrins represent a valuable class of ligands for G-quadruplex nucleic acids. Herein, we evaluate the binding of cationic porphyrins metallated with gold(iii) to G-quadruplex DNA and we compare it with other porphyrin derivatives. The G-quadruplex stabilization capacity and the selectivity of the various porphyrins were evaluated by biophysical and biochemical assays. The porphyrins were also tested as inhibitors of telomerase. It clearly appeared that the insertion of gold(iii) ion in the center of the porphyrin increases the binding affinity of the porphyrin for the G-quadruplex target. Together with modelling studies, it is possible to propose that the insertion of the square planar gold(iii) ion adds an extra positive charge on the complex and decreases the electron density in the porphyrin aromatic macrocycle, both properties being in favour of stronger electrostatic and π-staking interactions.

Mots clés: Quadruplex; Drug DNA interactions; Gold-porphyrin; Stacking; Quantum mechanics

Domaines: Chimie de coordination

Angélique Pipier, Aurore de Rache, Coralie Modeste, Samir Amrane, Emmanuelle Mothes-Martin, et al.. G-Quadruplex binding optimization by gold( iii ) insertion into the center of a porphyrin. Dalton Transactions, 2019, 48 (18), pp.6091-6099. ⟨10.1039/C8DT04703K⟩. ⟨hal-02140554⟩