Fragment Library Screening and Characterization with Biacore 4000

Fragment-based drug design is increasingly used to identify suitable structure scaffolds in drug discovery. Surface plasmon resonance biosensor is an attractive technique for the identification of low-affinity fragment compounds to drug targets due to low target consumption, high information content and high quality data. In this application note from GE Healthcare Life Sciences the Biacore 4000 with the Biacore 4000 LMW Extension Package was used to overcome the challenges posed by the low-millimolar affinity levels and low molecular weights that are typical for fragments. The novel evaluation tools produce quality data despite the challenges of fragment screening by supporting quick removal of aggregative and sticky binders, by efficient selection of prioritized fragments through high assay sensitivity and binding behavior analysis, and by facilitating affinity-based ranking despite the use of suboptimal sample concentrations and in the presence of secondary, unspecific binding.