Structure-reactivity relationships in the inactivation of elastase by β-sultams

Paul S. Hinchliffe, J. Matthew Wood, Andrew M. Davis, Rupert P. Austin, R. Paul Beckett, Michael I. Page

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46 Citations (Scopus)


N-Acyl-β-sultams are time dependent irreversible active site directed inhibitors of elastase. The rate of inactivation is first order with respect to β-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 1:1 enzyme inhibitor complex as a result of the active site serine being sulfonylated by the β-sultam. Ring opening of the β-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 β-sultams causes differences in the rates of inactivation by 4 orders of magnitude.

Original languageEnglish
Pages (from-to)67-80
Number of pages14
JournalOrganic and Biomolecular Chemistry
Issue number1
Early online date27 Nov 2002
Publication statusPublished - 7 Jan 2003


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