Looking for Patterns in Drug Screening

Founded in July 2001, Adaptive Screening Ltd. (ASL) of Cambridge, UK, is developing several miniaturized drug-profiling platforms. "Advances in high-throughput technologies coupled with the 'genomics explosion' have transferred the bottlenecks in drug discovery from compound synthesis and target identification to hit-to-lead profiling and target validation," comments Tony Cass, professor of chemical biology at the Imperial College of Science, Technology and Medicine in London, and one of ASL's c

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The company recently developed a novel, recombinant protein-based chip for identifying protein binding "signatures" in vitro.1 Candidate pharmaceutical compounds are passed over a prefabricated chip bearing an array of fluorescently labeled recombinant proteins, which, according to ASL, represent a significant number of the types of protein binding sites that pharmaceutical agents encounter in the human proteome. The fluorescent probes employ any of a variety of thermally stable protein scaffolds to display a series of different binding sites of relatively broad specificities. These probes are not specific for just one molecule, but rather, are capable of interacting with a range of different compounds with varying affinities and specificities. When a given protein in the array binds a pharmaceutical agent of interest, it may undergo conformational changes that reposition its fluorescent reporter, resulting in an increase or decrease in fluorescent signal.

ASL designed a detection system that monitors the overall pattern of ...

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