Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 135, Issue 36, Pages 13495-13501Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja405843r
Keywords
-
Categories
Funding
- Singapore Ministry of Education [ARC33/12]
- JSPS [23310158]
- Mukai Science and Technology Foundation, Tokyo, Japan
- Mochida Memorial Foundation for Medical and Pharmaceutical Research, Tokyo, Japan
- Grants-in-Aid for Scientific Research [23310158, 24651258] Funding Source: KAKEN
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available