Acylation versus sulfonylation in the inhibition of elastase by 3-oxo-β-sultams

β-Sultams are the sulfonyl analogues of β-lactams, and 3-oxo-β-sultams are both β-lactams and β-sultams and, therefore, susceptible to nucleophilic attack at either the acyl or the sulfonyl center. They are novel inactivators of serine enzymes. The second-order rate constant for the inactivation of elastase at pH 6 by N-benzyl-4,4-dimethyl-3-oxo-β-sultam is 768 M-1 s-1, which is 103-fold greater than that with N-benzoyl β-sultam. However, in contrast to N-acyl β-sultams, which sulfonylate the active site serine residue to form a sulfonate ester, 3-oxo-β-sultams inhibit the enzyme by acylation followed by slow deacylation to regenerate the active enzyme.