A CD Study of a Structure-Based Selection of <i>N</i>-Heterocyclic Bis-Carbene Gold(I) Complexes as Potential Ligands of the G-Quadruplex-Forming Human Telomeric hTel23 Sequence
Maria Marzano,
Filippo Prencipe,
Pietro Delre,
Giuseppe Felice Mangiatordi,
Gabriele Travagliante,
Luisa Ronga,
Gennaro Piccialli,
Michele Saviano,
Stefano D’Errico,
Diego Tesauro,
Giorgia Oliviero
Affiliations
Maria Marzano
Centro di Servizio di Ateneo per le Scienze e Tecnologie per la Vita (CESTEV), University of Napoli Federico II, Via Tommaso De Amicis 95, 80145 Napoli, Italy
Filippo Prencipe
Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via Licio Giorgieri 1, 34127 Trieste, Italy
Pietro Delre
Institute of Crystallography (IC), CNR, Via Amendola 122/O, 70126 Bari, Italy
Giuseppe Felice Mangiatordi
Institute of Crystallography (IC), CNR, Via Amendola 122/O, 70126 Bari, Italy
Gabriele Travagliante
Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy
Luisa Ronga
Institute of Analytical and Physical Chemistry for the Environment and Materials (IPREM-UMR 5254), Université de Pau Et Des Pays de L’Adour, E2S UPPA, CNRS, 64053 Pau, France
Gennaro Piccialli
Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy
Michele Saviano
Institute of Crystallography (IC), CNR, Via Vivaldi 43, 81100 Caserta, Italy
Stefano D’Errico
Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy
Diego Tesauro
Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy
Giorgia Oliviero
Department of Molecular Medicine and Medical Biotechnology, University of Napoli Federico II, Via Sergio Pansini 5, 80131 Napoli, Italy
Herein, we report the structure-based selection via molecular docking of four N-heterocyclic bis-carbene gold(I) complexes, whose potential as ligands for the hTel23 G-quadruplex structure has been investigated using circular dichroism (CD) spectroscopy, CD melting, and polyacrylamide gel electrophoresis (PAGE). The complex containing a bis(1,2,3,4,6,7,8,9-octahydro-11H-11λ3-pyridazino[1,2-a]indazol-11-yl) scaffold induces a transition from the hybrid (3 + 1) topology to a prevalent parallel G-quadruplex conformation, whereas the complex featuring a bis(2-(2-acetamidoethyl)-3λ3-imidazo[1,5-a]pyridin-3(2H)-yl) moiety disrupted the original G-quadruplex structure. These results deserve particular attention in light of the recent findings on the pathological involvements of G-quadruplexes in neurodegenerative diseases.
