Recognition of G-quadruplex DNA by triangular star-shaped compounds: with or without side chains? - Institut Curie Accéder directement au contenu
Article Dans Une Revue Chemistry - A European Journal Année : 2011

Recognition of G-quadruplex DNA by triangular star-shaped compounds: with or without side chains?

Résumé

We report the synthesis of two new series of triangular aromatic platforms, either with three aminoalkyl side chains (triazatrinaphthylene series, TrisK: six compounds), or without side chains (triazoniatrinaphthylene, TrisQ). The quadruplex-DNA binding behavior of the two series, which differ essentially by the localization of the cationic charges, was evaluated by means of FRET-melting and G4-FID assays. For the trisubstituted triazatrinaphthylenes (TrisK), the length of the substituents and the presence of terminal hydrogen-bond-donor groups (NH(2)) were shown to be crucial for ensuring a high quadruplex affinity (ΔT(1/2) values of up to 20 °C at 1 μM for the best candidate, TrisK3-NH) and selectivity versus duplex DNA. Subsequently, comparison of data collected on both the telomeric- and c-myc-quadruplex showed that the nonsubstituted TrisQ is even more efficient than TrisK3-NH, both in terms of quadruplex affinity (ΔT(1/2)=26 °C in K(+) buffer) and selectivity versus duplex DNA. Structural considerations conducted with the c-myc quadruplex indicate that both TrisK3-NH and TrisQ stack well onto the G-quartet but in an offset position, which might be influenced by the formation of multiple hydrogen bonds with the target in the former case. Finally, the nonsubstituted TrisQ displays a binding profile very similar to some of the best quadruplex binders, BRACO-19 and bisquinolinium 360A, used herein as references, and thereby represents a highly promising novel molecular design for quadruplex recognition.

Domaines

Chimie organique

Dates et versions

hal-00649221 , version 1 (07-12-2011)

Identifiants

Citer

Hélène Bertrand, Anton Granzhan, David Monchaud, Nicolas Saettel, Régis Guillot, et al.. Recognition of G-quadruplex DNA by triangular star-shaped compounds: with or without side chains?. Chemistry - A European Journal, 2011, 17 ((16)), pp.4529-39. ⟨10.1002/chem.201002810⟩. ⟨hal-00649221⟩
186 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More