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Analytical Chemistry

Screening made easier

July 31, 2006 | A version of this story appeared in Volume 84, Issue 31

Screening collections ofsmall molecules for bioactivity may get a little easier, thanks to a new, highly automated, and more efficient titration-based high-throughput screening protocol. The key is using automation to make it practical to screen compounds at multiple concentrations, instead of one concentration at a time. The technique, quantitative HTS (qHTS), was devised by James Inglese and coworkers of the NIH Chemical Genomics Center at the National Human Genome Research Institute as a way to more efficiently screen some of the 100,000 compounds collected by NIH's Molecular Libraries Screening Centers (Proc. Natl. Acad. Sci. USA 2006, 103, 11473). qHTS uses titration, low-volume dispensing, high-sensitivity detectors, robotic plate-handling, and data analysis tools to make multiconcentration analysis feasible. Its advantages include obtaining structure-activity relationship data directly from individual screens, which is not possible with conventional screening, and reducing false negatives (bioactive compounds that would have been missed by conventional HTS) and false positives. The group used qHTS to measure the pyruvate kinase activity of 61,000 compounds at seven or more concentrations across 368 1,536-well microtiter plates in 30 hours.


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