From Model Complexes to Metalloprotein Inhibition: A Synergistic Approach to Structure‐Based Drug Discovery

Abstract

A happy marriage: The combination of synthetic model chemistry with computational conformational analysis has revealed the binding of an inhibitor to a medically important metalloenzyme. [(TpPh,Me)Zn(mbt)] (TpPh,Me=hydrotris(3,5-phenylmethylpyrazolyl)borate, mbt=2-methoxybenzenethiol) was used to template the conformation of a known inhibitor in the active site of the metalloenzyme, as shown by the green ligand inside the active site of the protein (the ZnII ion is shown in purple).