論文 - 詳細
| RRC ID | 43143 |
|---|---|
| 著者 | Liu X, Takahashi H, Harada Y, Ogawara T, Ogimura Y, Mizushina Y, Saneyoshi M, Yamaguchi T. |
| タイトル | 3'-Azido-2',3'-dideoxynucleoside 5'-triphosphates inhibit telomerase activity in vitro, and the corresponding nucleosides cause telomere shortening in human HL60 cells. |
| ジャーナル | Nucleic Acids Res |
| Abstract |
Telomerase adds telomeric DNA repeats to the ends of linear chromosomal DNA. 3'-Azido-3'-deoxythymidine 5'-triphosphate (AZTTP) is a known telomerase inhibitor. To obtain more selective and potent inhibitors that can be employed as tools for studying telomerase, we investigated the telomerase-inhibitory effects of purine nucleosides bearing a 3'-down azido group: 3'-azido-2',3'-dideoxyguanosine (AZddG) 5'-triphosphate (AZddGTP), 3'-azido-2',3'-dideoxy-6-thioguanosine (AZddSG) 5'-triphosphate (AZddSGTP), 3'-azido-2',3'-dideoxyadenosine (AZddA) 5'-triphosphate (AZddATP) and 3'-azido-2',3'-dideoxy-2-aminoadenosine (AZddAA) 5'-triphosphate (AZddAATP). Of these, AZddGTP showed the most potent inhibitory activity against HeLa cell telomerase. AZddGTP was significantly incorporated into the 3'-terminus of DNA by partially purified telomerase. However, AZddGTP did not exhibit significant inhibitory activity against DNA polymerases alpha and delta, suggesting that AZddGTP is a selective inhibitor of telomerase. We also investigated whether long-term treatment with these nucleosides could alter telomere length and growth rates of human HL60 cells in culture. Southern hybridization analysis of genomic DNA prepared from cells cultured in the presence of AZddG and AZddAA revealed reproducible telomere shortening. |
| 巻・号 | 35(21) |
| ページ | 7140-9 |
| 公開日 | 2007-1-1 |
| DOI | 10.1093/nar/gkm859 |
| PII | gkm859 |
| PMID | 17942424 |
| PMC | PMC2175342 |
| MeSH | Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Cell Proliferation / drug effects DNA / chemistry DNA / metabolism Dideoxyadenosine / analogs & derivatives Dideoxyadenosine / chemistry Dideoxyadenosine / pharmacology Dideoxynucleosides / chemistry Dideoxynucleosides / pharmacology* Dideoxynucleotides / chemistry Dideoxynucleotides / pharmacology* Enzyme Inhibitors / chemistry Enzyme Inhibitors / pharmacology HL-60 Cells HeLa Cells Humans Telomerase / antagonists & inhibitors* Telomere / chemistry Telomere / metabolism* Zidovudine / chemistry Zidovudine / pharmacology |
| IF | 11.502 |
| 引用数 | 31 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa(RCB0007) HL60(RCB0041) |