Fragment-based drug design has been successfully applied to challenging targets where
the detection of the weak protein-ligand interactions is a key element. H-1 saturation
transfer difference (STD) NMR spectroscopy is a powerful technique for this work but
it requires pure homogeneous proteins as targets. Monoclonal antibody (mAb)-relayed
N-15-GS STD spectroscopy has been developed to resolve the problem of protein mixtures
and impure proteins. A N-15-labelled target-specific mAb is selectively irradiated
and the saturation is relayed through the target to the ligand. Tests on the anti-Gal-1
mAb/Gal-1/lactose system showed that the approach is experimentally feasible in a
reasonable time frame. This method allows detection and identification of binding
molecules directly from a protein mixture in a multicomponent system.
