Structure–reactivity relationships in the inactivation of elastase by β-sultams
- 27 November 2002
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Organic & Biomolecular Chemistry
- Vol. 1 (1) , 67-80
- https://doi.org/10.1039/b208079f
Abstract
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 l ∶ l 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.Keywords
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