Fragment Screening

Sensitivity and throughput of current SPR instrumentation enables this technology to be used for screening of large libraries of fragments or compounds. The development of SPR-based fragment screening has several advantages over current X-ray and NMR methods. Firstly, the protein consumption for SPR methods is at least 10-fold less than other biochemical and biophysical fragment screening methods. Secondly, SPR assays can be developed more quickly than other methods. Thirdly, SPR methods provide a richer characterisation of each fragment by providing the kinetics and thermodynamics of binding that NMR and X-ray cannot provide. For example, SPR will not only identify which fragments bind but allow one to identify fragments with slow-off set kinetics in a predominately enthalpic manner, properties which may make better starting points for optimization. The combination of SPR screening with chemoinformatics can overcome the need for protein structure in fragment-based drug discovery.

Fragment Screening by Surface Plasmon Resonance. Iva Navratilova and Andrew L. Hopkins, ACS Med. Chem. Lett. (2010), 1(1), 44-48