Halo enol lactone inhibitors of chymotrypsin: Burst kinetics and enantioselectivity of inactivation

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Abstract

Burst kinetics in the inactivation of α-chymotrypsin by halo enol lactones 1 and 2 was observed. These results are consistent with a kinetic scheme that includes partitioning of the first acyl enzyme between transient inhibition and permanent inactivation. Partition ratios were estimated from the measured rates of the irreversible inactivation and the rates of deacylation of the second acyl enzyme. Halo enol lactones with a large burst resulted in small partition ratios, indicating a high potency of inactivation. We also observed enantioselectivity in the burst of inactivation such that the R enantiomer of lactone 1 showed a large burst, while the S enantiomer showed a little burst. This suggests that it is the R enantiomer whose binding is better suited for the covalent derivatization of the enzyme, or whose reactive halomethyl group is in an unfavorable position for the hydrolysis by water.

Original languageEnglish (US)
Pages (from-to)1335-1342
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume178
Issue number3
DOIs
StatePublished - Aug 15 1991

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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