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 pi-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.
Solution structure of an intramolecular (3+1) human telomeric G-quadruplex bound to a telomestatin derivative.,Chung WJ, Heddi B, Tera M, Iida K, Nagasawa K, Phan AT J Am Chem Soc. 2013 Aug 2. PMID:23909929
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↑ Chung WJ, Heddi B, Tera M, Iida K, Nagasawa K, Phan AT. Solution structure of an intramolecular (3+1) human telomeric G-quadruplex bound to a telomestatin derivative. J Am Chem Soc. 2013 Aug 2. PMID:23909929 doi:10.1021/ja405843r