Spatial requirements of the antagonist binding site of the NK2 receptor

Computer-aided modelling has been used to identify a putative antagonist binding site in the tachykinin NK2 receptor. In order to validate the implied spatial requirements for this region, a series of compounds, based on the potent antagonist GR 149861 have been synthesised and their binding affinities established. Our findings suggest the presence of a large hydrophobic cavity in the putative binding crevice of GR 149861.