Constitutional Dynamic Inhibition/Activation of Carbonic Anhydrases

In this review we consider one important member of the metalloenzymes family, the carbonic anhydrase (CA), involved in the treatment of several common diseases. Different approaches have emerged to regulate the activity of CA, mostly acting on the inner catalytic active site or outer microenvironment of the enzyme, leading to inhibition or activation of CA. In recent years, gradually increased attention has focused on the adoption of constitutional dynamic chemistry (CDC) strategies for the screening and discovery of potent inhibitors or activators. The participation of reversible covalent bonds enabled the enzyme itself to select the optimal ligands obtained from diverse building blocks with comparatively higher degree of variety, resulting in the fittest recognition of enzyme ligands from complex dynamic systems. With the increasing implementation of CDC for enzyme targets, it shows great potential for drug discovery or CO₂ capture applications.