New peptide boronic acid inhibitors of thrombin

Peptides containing α-amino boronic acids bind to the active site of serine protease, forming highly effective inhibitors. The trigonal boron in these compounds contain a vacant 2p orbital that easily reacts with nucleotides such as the Ser hydroxyl or the His imidazole at the catalytic site of the enzyme to give a tetrahedral transition-state boron adduct as shown in Figure 1, similar to that observed with aldehydes which is stabilised in an analogous manner to the transition state of the substrate, by interactions with secondary binding sites (e.g. oxyanion binding pocket)