Structure-activity relationships in the inactivation of elastase by β-sultam

N-Acyl--sultams are time dependent irreversible active site directed inhibitors of elastase. The rate of inactivation is first order with respect to -sultam concentration and the second order rate constants show a similar dependence on pH to that for the hydrolysis of a peptide substrate. Inactivation is due to the formation of a stable l l enzyme inhibitor complex as a result of the active site serine being sulfonylated by the -sultam. Ring opening of the -sultam occurs by S–N fission in contrast to the C–N fission observed in the acylation of elastase by N-acylsulfonamides. Structure–activity effects are compared between sulfonylation of the enzyme and alkaline hydrolysis. Variation in 4-alkyl and N-substituted -sultams causes differences in the rates of inactivation by 4 orders of magnitude