Fragment screening by biochemical assay

Abstract

The use of high concentration biochemical assays to identify weak binding fragment molecules can be an effective method to identify novel starting points for medicinal chemistry programmes. The combination of a high-quality fragment library with sensitive biochemical screening methods is a viable alternative to the more commonly used fragment screening methods such as nuclear magnetic resonance screening or high-throughput X-ray crystallography. Notably, there are a number of literature reports where fragment molecules have been identified by a high concentration biochemical assay. The use of high concentration screening of fragments using a portfolio of single-molecule fluorescence correlation spectroscopy detection techniques to ensure the highest reproducibility and sensitivity have been demonstrated, as well as the use of and X-ray crystallography to determine the binding mode of active fragments.