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Binding Modes and Selectivity of Ruthenium Complexes to Human Telomeric DNA G-Quadruplexes

par Rubio-Magnieto, Jenifer;Kajouj, Sofia ;Di Meo, Florent;Fossépré, Mathieu;Trouillas, Patrick;Norman, Patrick;Linares, Mathieu;Moucheron, Cécile ;Surin, Mathieu
Référence Chemistry, 24, 58, page (15577-15588)
Publication Publié, 2018

Article révisé par les pairs

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Résumé :

Metal complexes constitute an important class of DNA binders. In particular, a few ruthenium polyazaaromatic complexes are attractive as “light switches” because of their strong luminescence enhancement upon DNA binding. In this paper, a comprehensive study on the binding modes of several mononuclear and binuclear ruthenium complexes to human telomeric sequences, made of repeats of the d(TTAGGG) fragment is reported. These DNA sequences form G-quadruplexes (G4s) at the ends of chromosomes and constitute a relevant biomolecular target in cancer research. By combining spectroscopy experiments and molecular modelling simulations, several key properties are deciphered: the binding modes, the stabilization of G4 upon binding, and the selectivity of these complexes towards G4 versus double-stranded DNA. These results are rationalized by assessing the possible deformation of G4 and the binding free energies of several binding modes via modelling approaches. Altogether, this comparative study provides fundamental insights into the molecular recognition properties and selectivity of Ru complexes towards this important class of DNA G4s.