Boronic Esters as Enzyme Inhibitors

As discussed in the Introduction, boronic ester formation is a readily reversible process. Therefore, most of the inhibitors are used in their free acid form. However, if one uses a diol that can form a very tight covalent adduct with a boronic acid, one can make an ester inhibitor that is stable enough to hydrolysis on the time scale needed for the inhibitory activities. 

Pinacol is the other diol suitable for preparation of boronic ester inhibitors. In a separate study, a pinacol-protected boronic ester of Ac-Thr-Glu-Leu-Lys-Glu-boroLeu-OH TFA (DPC-AB9144-00) was designed and synthesized as a boron-modified pep-tidyl mimetic of the bovine viral diarrhea virus (BVDV) NS4A/NS4B cleavage site and shown to be an effident inhibitor of the BVDV NS3 protease [55]. 

---