title: Targeting human telomeric higher-order DNA: dimeric G-quadruplex units serve as preferred binding site.
abstract: Long human telomeric fragments can form stable, higher-order G-quadruplex structures, recently identified in human cells, which are potential drug targets. However, there are very few examples of ligand binding to higher-order G-quadruplexes, and all the reported ligands are proposed to bind at the cleft between two G-quadruplexes. Here we report that zinc-finger-like chiral supramolecular complexes prefer binding to higher-order G-quadruplexes over a single G-quadruplex, with ∼200-fold higher selectivity. To our knowledge, this is the first example of a ligand that can distinguish higher-order G-quadruplexes from a single G-quadruplex with such high selectivity. Further studies indicate that the nanosized chiral complex would bind to two well-matched G-quadruplex units, instead of binding at the cleft between the two G-quadruplexes. These results provide new insights into the targeting of higher-order G-quadruplex ligands. Our work illustrates that dimeric G-quadruplex units can be ligand-preferred binding sites.
authors.affiliation: Division of Biological Inorganic Chemistry, State Key Laboratory of Rare Earth Resource Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun, Jilin 130022, China.
authors.forename: Chuanqi
authors.initials: C
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Jinsong
authors.initials: J
authors.lastname: Ren
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Qu
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D019281:Dimerization; D005453:Fluorescence; D054856:G-Quadruplexes; D006801:Humans; D016615:Telomere; D013816:Thermodynamics; D014466:Ultraviolet Rays
chemical_list: D004247:DNA