title: A chiral wedge molecule inhibits telomerase activity.
abstract: In addition to the Watson-Crick double helix, secondary DNA structures are thought to play important roles in a variety of biological processes. One important example is the G-quadruplex structure that is formed at the chromosome ends, which inhibits telomerase activity by blocking its access to telomeres. G-quadruplex structures represent a new class of molecular targets for DNA-interactive compounds that may be useful to target telomeres. Here, we reported the first example of enantioselective recognition of quadruplex DNA by a chiral cyclic helicene. We propose a new ligand-binding cleft between two telomeric human G-quadruplexes linked by a TTA linker. We found that the cyclic helicene M1 exhibited potent inhibitory activity against telomerase.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku Kyoto 606-8502, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Shinohara
authors.forename: Yuta
authors.initials: Y
authors.lastname: Sannohe
authors.forename: Shuji
authors.initials: S
authors.lastname: Kaieda
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hideji
authors.initials: H
authors.lastname: Osuga
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tahara
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawase
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043542:DNA, Z-Form / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D054856:G-Quadruplexes / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D008958:Models, Molecular; D011083:Polycyclic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013237:Stereoisomerism; D013379:Substrate Specificity; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D043542:DNA, Z-Form; D004791:Enzyme Inhibitors; D011083:Polycyclic Compounds; C031660:helicenes; D004247:DNA; D019098:Telomerase