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

-Sultams are the sulfonyl analogues of
-lactams, and 3-oxo- -sultams are both
-lactams and -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- -sultam is 768 M-1 s-1, which is 103-fold greater than However, in contrast to N-acyl -sultams, which sulfonylate the active site serine residue to form a sulfonate ester, 3
acylation followed by slow deacylation to regenerate the active enzyme.