Details

Autor(en) / Beteiligte

• Chung, Wan Jun
• Heddi, Brahim
• Tera, Masayuki
• Iida, Keisuke
• Nagasawa, Kazuo
• Phan, Anh Tuân

Titel

Solution Structure of an Intramolecular (3 + 1) Human Telomeric G‑Quadruplex Bound to a Telomestatin Derivative

Ist Teil von

• Journal of the American Chemical Society, 2013-09, Vol.135 (36), p.13495-13501

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• Guanine-rich human telomeric DNA can adopt secondary structures known as G-quadruplexes, which can be targeted by small molecules to achieve anticancer effects. So far, the structural information on complexes between human telomeric DNA and ligands is limited to the parallel G-quadruplex conformation, despite the high structural polymorphism of human telomeric G-quadruplexes. No structure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here we present the first high-resolution structure of the complex between an intramolecular (3 + 1) human telomeric G-quadruplex and a telomestatin derivative, the macrocyclic hexaoxazole L2H2-6M(2)OTD. This compound is observed to interact with the G-quadruplex through π-stacking and electrostatic interactions. This structural information provides a platform for the design of topology-specific G-quadruplex-targeting compounds and is valuable for the development of new potent anticancer drugs.