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. 2014 Jan 20;53(4):999-1002.
doi: 10.1002/anie.201308063. Epub 2013 Dec 16.

Solution structure of a G-quadruplex bound to the bisquinolinium compound Phen-DC(3)

Wan Jun Chung  1 , Brahim Heddi, Florian Hamon, Marie-Paule Teulade-Fichou, Anh Tuân Phan
Affiliations

Solution structure of a G-quadruplex bound to the bisquinolinium compound Phen-DC(3)

Wan Jun Chung et al. Angew Chem Int Ed Engl. .

Abstract

Phen-DC3 is a highly promising compound that specifically targets G-quadruplexes, with potent biological effects observed in vivo. We used NMR spectroscopy to solve the structure of the complex formed between Phen-DC3 and an intramolecular G-quadruplex derived from the c-myc promoter. Structural information revealed that Phen-DC3 interacts with the quadruplex through extensive π-stacking with guanine bases of the top G-tetrad. On the basis of our structure, modifications are proposed for the development of this compound for selective targeting of a specific G-quadruplex conformation.

Keywords: G-quadruplex DNA; NMR spectroscopy; bisquinolinium ligands; drug design; π interactions.

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