Mechanism-based proteinase inhibitors: a critical review.

The efficacy of a mechanism-based enzyme inhibitor depends not only on the rate of covalent modification of the target enzyme, but also on the affinity with which the enzyme binds the inhibitor before covalent bond formation. Since proteinases have binding regions that extend many residues beyond the scissile peptide bond, specific and potent mechanism-based inhibitors of this class of enzyme can only be obtained by incorporating features of those secondary binding sites into the inhibitor molecule.