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Charles A Wartchow, Frank Podlaski, Karen Rowan, Xiaolei Zhang, Kuo-Sen Huang, David Mark
Discovery Technologies, Hoffman-La Roche Inc., Nutley, NJ
Biosensor-based fragment screening is an emerging tool in the drug discovery process. This method is advantageous over many biochemical methods because primary hits can be distinguished from non-specific or non-ideal interactions by examining binding profiles and responses, resulting in reduced false-positive rates. The FortéBio RED systems are based on biolayer interferometry (BLI), a technique that generates an interference pattern by monitoring visible light reflected from two surfaces on a fiber-optic biosensor. This system was validated for small molecule detection with models systems and well-characterized targets. Fragment screening was validated with the Maybridge RO500 library, and several screens with challenging targets involved in protein-protein interactions were performed. Hits obtained from BLI were compared to results obtained in biochemical screens, and hits were further characterized by both BLI and SPR.