[Au(9-methylcaffein-8-ylidene) 2 ] + /DNA Tel23 System: Solution, Computational, and Biological Studies

Francesco Papi; Carla Bazzicalupi; Marta Ferraroni; Lara Massai; Benoit Bertrand; Paola Gratteri; Donato Colangelo; Luigi Messori

doi:10.1002/chem.201702854

Article dans une revue

[Au(9-methylcaffein-8-ylidene) 2 ] + /DNA Tel23 System: Solution, Computational, and Biological Studies

Francesco Papi ^{1, 2, 3} Carla Bazzicalupi ^{1, *} Marta Ferraroni ¹ Lara Massai ¹ Benoit Bertrand ⁴ Paola Gratteri ^{2, 3, *} Donato Colangelo ⁵ Luigi Messori ^{1, *}

* Auteur correspondant

1 Dipartimento di Chimica ‘Ugo Schiff', Università degli Studi di Firenze

2 NEUROFARBA - Dipartimento di Neuroscienze, Psicologia, Area del Farmaco, Salute del Bambino, Università degli Studi di Firenze

3 Laboratory of Molecular Modeling Cheminformatics & QSAR

4 ICMUB - Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon]

5 Dipartimento di Scienze della Salute

Università degli Studi del Piemonte Orientale-Amedeo Avogadro (ITALY)

Abstract : Physicochemical methods have been used to investigate interactions occurring in solution between the dicarbene gold(I) complex [Au(9‐methylcaffein‐8‐ylidene)2]BF4 (AuNHC) and a human telomeric DNA sequence, namely Tel23. Circular dichroism measurements allow identification of the conformational changes experienced by Tel23 upon interaction with AuNHC, and the respective binding stoichiometries and constants were determined. Computational studies provide a good link between previous crystallographic results of the same system and the present solution data, offering an exhaustive description of the inherent noncovalent metallodrug–DNA interactions. Remarkably, we found that a preformed AuNHC/Tel23 adduct is capable of producing strong and selective inhibition of the enzyme telomerase. The latter feature is mechanistically relevant and might account for the conspicuous in vitro anticancer properties of the investigated dicarbene gold(I) complex.

Keywords : antitumor agents circular dichroism DNA structures gold carbenes G-quadruplexes telomerase human telomeric dna g-quadruplex structures k+ solution circular-dichroism structural basis anticancer agents ligand-binding complexes sequence density

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Article dans une revue

Domaine :

Chimie

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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01856650
Contributeur : Icmub - Université de Bourgogne <>
Soumis le : lundi 13 août 2018 - 10:57:49
Dernière modification le : vendredi 13 novembre 2020 - 09:08:03

[Au(9-methylcaffein-8-ylidene) 2 ] + /DNA Tel23 System: Solution, Computational, and Biological Studies

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