Using in situ click chemistry and X-ray crystallography of ligand-receptor complexes we have discovered modulators of two biological targets :(1) a bacterial transcription factor called EthR which controls the bioactivation of ethionamide and prothionamide,two important antituberculous antibiotics and(2) IDE(insulin degrading enzyme) a remarkable peptidase that cleaves a broad range of bioactive peptides including Insulin and beta-amyloid peptide.We will show how the compounds have been discovered,how they bind to their targets and modify their biological activity.Numerous receptor-ligand complexes have been crystallised and solved by X-ray diffraction for both series.Structure-Activity-Relationships will be presented and discussed.