A Chiral Wedge Molecule Inhibits Telomerase Activity
| Autor: | Takashi Kawase, Toshikazu Bando, Shuji Kaieda, Hidetoshi Tahara, Yuta Sannohe, Yan Xu, Ken-ichi Tanaka, Hiroshi Sugiyama, Hideji Osuga, Ken-ichi Shinohara |
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| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular Telomerase Stereochemistry Biochemistry Catalysis Substrate Specificity Jurkat Cells chemistry.chemical_compound Colloid and Surface Chemistry DNA Z-Form Humans Molecule Polycyclic Compounds heterocyclic compounds Enzyme Inhibitors Base Sequence Enantioselective synthesis Stereoisomerism DNA General Chemistry Telomere G-Quadruplexes chemistry Helicene Helix Linker |
| Zdroj: | Journal of the American Chemical Society. 132:3778-3782 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja908897j |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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