Methods for modulation and inhibition of telomerase
US6004939A · kind A · utility
Assignees
Inventors
Key dates
| Filing date | Jun 20, 1997 |
| Grant date | Dec 21, 1999 |
| Priority date | — |
| Expiry date | Jun 20, 2017 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07H19/14
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
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 affectin…
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