Fragment screening techniques

More than 2,000 potential replacements for the bromophenyl or pyridyl groups were then screened using the NMR-screening technique. Several fragments were identified which caused chemical shift changes in the desired binding site of the protein, amongst them indole (7) and 2-phenylimidazole... 

There are various methods to conduct a fragment screening campaign. The most commonly utilized methods include various NMR techniques, mass spectrometry, SPR, and biochemical screens. X-ray crystallization is a preferred method since it provides a binding conformation, but can only be used when the target protein is well behaved. Various calorimetry techniques have also been used for fragment screening, but these have been less commonly utilized. The merits of each method have been discussed in the literature (26) and will not be outlined here. 

In recent years there have been encouraging advances in screening technologies suitable for fragment screening. Even for an established method such as NMR, new techniques have been developed and put into practice at various companies that have expanded the scope of targets for FBDD. For example,... 

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