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.