Peroxides as oxidative enzyme inhibitors: mechanism-based inhibition of a cysteine protease by an amino acid ozonide

P H Dussault; A D George; T K Trullinger

doi:10.1016/s0960-894x(99)00563-6

Peroxides as oxidative enzyme inhibitors: mechanism-based inhibition of a cysteine protease by an amino acid ozonide

Bioorg Med Chem Lett. 1999 Nov 15;9(22):3255-8. doi: 10.1016/s0960-894x(99)00563-6.

Authors

P H Dussault¹, A D George, T K Trullinger

Affiliation

¹ Department of Chemistry, University of Nebraska-Lincoln, 68588-0304, USA.

PMID: 10576698
DOI: 10.1016/s0960-894x(99)00563-6

Abstract

A stable ozonide derived from Cbz-L-Phe accomplishes rapid and stoichiometric inhibition of papain at less than 100 microM concentration under conditions where formation of the corresponding aldehyde is negligible. Oxidation of the active site thiolate by the bound peroxide is believed to lead to formation of an inactive sulfenate or sulfenic acid. Reduction of the ozonide in excess DMSO provides a convenient method for in situ generation of a peptide aldehyde.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amino Acids / chemistry*
Cysteine Proteinase Inhibitors / pharmacology*
Oxidation-Reduction
Ozone / chemistry*
Peroxides / pharmacology*

Substances

Amino Acids
Cysteine Proteinase Inhibitors
Peroxides
Ozone