Rapid identification and characterization of hammerhead-ribozyme inhibitors using fluorescence-based technology
| Autor: | Jörg S. Hartig, Dmitry A. Samarsky, Andreas Tauer, Michael R. Green, Michael Famulok, Nicolas Piganeau, Julian Davies, Andreas Jenne |
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| Rok vydání: | 2001 |
| Předmět: |
Hammerhead ribozyme
Drug Evaluation Preclinical Biomedical Engineering Bioengineering Cleavage (embryo) Applied Microbiology and Biotechnology Catalysis Structure-Activity Relationship In vivo Enviomycin RNA Catalytic Base Sequence biology Ribozyme Cooperative binding RNA biology.organism_classification Small molecule In vitro Anti-Bacterial Agents Kinetics Biochemistry Drug Design ddc:540 biology.protein Nucleic Acid Conformation Molecular Medicine Biotechnology |
| Zdroj: | Nature Biotechnology. 19:56-61 |
| ISSN: | 1546-1696 1087-0156 |
| DOI: | 10.1038/83513 |
| Popis: | The ability to rapidly identify small molecules that interact with RNA would have significant clinical and research applications. Low-molecular-weight molecules that bind to RNA have the potential to be used as drugs. Therefore, technologies facilitating the rapid and reliable identification of such activities become increasingly important. We have applied a fluorescence-based assay to screen for modulators of hammerhead ribozyme (HHR) catalysis from a small library of antibiotic compounds. Several unknown potent inhibitors of the hammerhead cleavage reaction were identified and further characterized. Tuberactinomycin A, for which positive cooperativity of inhibition in vitro was found, also reduced ribozyme cleavage in vivo. The assay is applicable to the screening of mixtures of compounds, as inhibitory activities were detected within a collection of 2,000 extracts from different actinomycete strains. This approach allows the rapid, reliable, and convenient identification and characterization of ribozyme modulators leading to insights difficult to obtain by classical methodology. |
| Databáze: | OpenAIRE |
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