发明名称 |
Methods for modulation and inhibition of telomerase |
摘要 |
It was found that normal human stem cells produce a regulated non-processive telomerase activity, while cancer cells produce a processive telomerase activity. Nucleotide analogs, such as 7-deaza-2'-deoxyquanosine-5'-triphosphate (7-deaza-dGTP) were found to be substrates for processive telomerase and incorporated into telomeric sequence. The incorporation of this nucleotide subsequently affected the processivity of telomerase, converting processive telomerase to non-processive telomerase. The incorporation of this nucleotide analogs was also found to inhibit formation of G-quartets by telomeric sequence. Other methods for converting cancer processive telomerase to the more benign non-processive telomerase include partially cleaving the telomerase RNA. The nucleoside analogs were found to be capable of a variety of activities including mediating allosteric-like inhibition of telomerase, premature termination and shortening of telomeric DNA, destabilization of telomeric structure and function and eventually cell death. Understanding the mechanisms of telomerase modulation by the 7-deazanucleotides has allowed the design of new telomerase inhibitors, modulators and agents for affecting telomere structure and function. These discoveries have application in the treatment of cancer.
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申请公布号 |
US6004939(A) |
申请公布日期 |
1999.12.21 |
申请号 |
US19970879457 |
申请日期 |
1997.06.20 |
申请人 |
CTRC RESEARCH FOUNDATION BOARD OF REGENTS;THE UNIVERSITY OF TEXAS SYSTEM |
发明人 |
CHEN, SHIH-FONG;MAINE, IRA;KERWIN, SEAN M.;FLETCHER, TERACE M.;SALAZAR, MIQUEL;MAMIYA, BLAIN;WAJIMA, MAKOTO;WINDLE, BRADFORD E. |
分类号 |
A61K31/70;C07H19/14;(IPC1-7):A61K31/70 |
主分类号 |
A61K31/70 |
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