Template-Assembled Synthetic G-Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies.

A new biomol. device for investigating the interactions of ligands with constrained DNA quadruplex topologies, using surface plasmon resonance (SPR), is reported. Biomol. systems contg. an intermol.-like G-quadruplex motif 1 (parallel G-quadruplex conformation), an intramol. G-quadruplex 2, and a duplex DNA 3 have been designed and developed. The method is based on the concept of template-assembled synthetic G-quadruplex (TASQ), whereby quadruplex DNA structures are assembled on a template that allows precise control of the parallel G-quadruplex conformation. Various known G-quadruplex ligands have been used to investigate the affinities of ligands for intermol. 1 and intramol. 2 DNA quadruplexes. As anticipated, ligands displaying a $π$-stacking binding mode showed a higher binding affinity for intermol.-like G-quadruplexes 1, whereas ligands with other binding modes (groove and/or loop binding) showed no significant difference in their binding affinities for the two quadruplexes 1 or 2. In addn., the present method has also provided information about the selectivity of ligands for G-quadruplex DNA over the duplex DNA. A numerical parameter, termed the G-quadruplex binding mode index (G4-BMI), has been introduced to express the difference in the affinities of ligands for intermol. G-quadruplex 1 against intramol. G-quadruplex 2. The G-quadruplex binding mode index (G4-BMI) of a ligand is defined as follows: G4-BMI = KDintra/KDinter, where KDintra is the dissocn. const. for intramol. G-quadruplex 2 and KDinter is the dissocn. const. for intermol. G-quadruplex 1. In summary, the present work has demonstrated that the use of parallel-constrained quadruplex topol. provides more precise information about the binding modes of ligands. [on SciFinder(R)]

Références

Titre
Template-Assembled Synthetic G-Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies.
Type de publication
Article de revue
Année de publication
2010
Revue
Chem. - A Eur. J.
Volume
16
Pagination
6106–6114, S6106/1–S6106/16
ISSN
0947-6539
Soumis le 12 avril 2018