Identification of a series of potent telomerase inhibitors using a time-resolved fluorescence-based assay

✍ Scribed by Lance A. Bare; Lan Trinh; Shung Wu; James J. Devlin

• Book ID: 101265614
• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 304 KB
• Volume: 43
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/(sici)1098-2299(199802)43:2<109::aid-ddr4>3.0.co;2-o

✦ Synopsis

A high-throughput, nonradioactive telomerase assay using a europium-labeled oligonucleotide probe and time-resolved fluorescence has been developed to detect PCR-amplified telomerase products. The use of a thermally activated TAQ polymerase, rather than a wax barrier, to implement a PCR hot-start facilitated the use of laboratory automation equipment. Results obtained with this high-throughput protocol correlate well with those obtained with the TRAP protocol. Screening a set of 125,000 compounds from the Berlex library, we identified a set of isothiazolone-containing telomerase inhibitors. The most potent of these inhibitors have submicromolar IC 50 values and may be reacting with a telomerase thiol. These compounds may be useful tools to evaluate the effects of telomerase in cancer cells.