A chiral wedge molecule inhibits telomerase activity.
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.
Shinohara
Ken-ichi
K
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku Kyoto 606-8502, Japan.
Sannohe
Yuta
Y
Kaieda
Shuji
S
Tanaka
Ken-ichi
K
Osuga
Hideji
H
Tahara
Hidetoshi
H
Xu
Yan
Y
Kawase
Takashi
T
Bando
Toshikazu
T
Sugiyama
Hiroshi
H
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
D043542:DNA, Z-Form; D004791:Enzyme Inhibitors; D011083:Polycyclic Compounds; C031660:helicenes; D004247:DNA; D019098:Telomerase