Illuminating? The enzyme that gives fireflies their glow might not be ideal for drug testing.
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A screening method commonly used drug based on the enzyme that gives fireflies their glow may be defective. Researchers from the National Institutes of Health (NIH) found that certain compounds - one in clinical trials for cystic fibrosis and other conditions -. Luminescence is just an artifact
For decades, researchers used firefly luciferase - the protein that makes insect light - as a so-called reporter enzyme. Take the example of cystic fibrosis: Some forms of the disease result when a "stop sign" gene prevents the body's cells to a full version of the protein cystic fibrosis An effective drug should allow. cells to ignore this stop signal such that the full length protein can be produced. to screen for such drugs, scientists bind DNA firefly luciferase at the end of the gene for cystic fibrosis. If a drug works, the complete protein cystic fibrosis will be made -. And scientists see a glimmer
But Douglas Auld, an expert on screening high drug flow to the Chemical Genomics Center NIH, found a problem with this approach. His team examined an experimental drug called PTC124, the firefly luciferase assay was identified as a promising candidate for the treatment of forms of cystic fibrosis and is currently being tested in clinical trials stop-sign. The researchers found that PTC124, and many compounds related to it, bind to the protein luciferase firefly, causing it to brighter than normal. And that makes the drug appears more effective than it really is, said Auld. When the researchers tested PTC124 using another luminescent enzyme with a different structure, they saw no light at all.
Co-author James Inglese, deputy director of the Chemical Genomics Center, said the work emphasizes the importance of using more than one test for drug research. Most of the compounds identified in the screen of the firefly luciferase do not interact in this way with luciferase, he said, but it is important to make sure.
John Babiak, vice president of drug discovery technologies at PTC Therapeutics in South Plainfield, New Jersey, which is developing and testing PTC124, shrugs NIH work. "You get positive and artifacts false" in any dosage, he said. Babiak says his company found that PTC124 appears promising in a number of other tests that do not use the firefly luciferase and in the animal testing and clinical trials. the fact that PTC124 binds to luciferase, he said, "has nothing to do with the fact that it is a good drug." (NIH researchers do not call not question the clinical and animal PTC124 results.)
Keith Wood, research director at Promega Corp. Madison, Wisconsin, and an expert in bioluminescent assays, agrees that work should not undermine NIH PTC124. But the new study, he said, provides an important caveat for researchers using any enzyme not only firefly luciferase, to report on the biological activity. "no tools for screening is perfect ' he said.
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