title: Solution structure of an intramolecular (3 + 1) human telomeric G-quadruplex bound to a telomestatin derivative.
abstract: 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.
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University , Singapore.
authors.forename: Wan Jun
authors.initials: WJ
authors.lastname: Chung
authors.forename: Brahim
authors.initials: B
authors.lastname: Heddi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tera
authors.forename: Keisuke
authors.initials: K
authors.lastname: Iida
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagasawa
authors.forename: Anh Tuân
authors.initials: AT
authors.lastname: Phan
mesh_terms: D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry*; D012996:Solutions; D016615:Telomere / Q000737:chemistry*
chemical_list: D010080:Oxazoles; D012996:Solutions; C431888:telomestatin