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

Patrick H. Dussault; A. Denise George; Tony 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

Patrick H. Dussault, A. Denise George, Tony K. Trullinger

Chemistry

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

A stable ozonide derived from Cbz-L-Phe accomplishes rapid and stoichiometric inhibition of papain at less than 100 μM 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.

Original language	English (US)
Pages (from-to)	3255-3258
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	9
Issue number	22
DOIs	https://doi.org/10.1016/S0960-894X(99)00563-6
State	Published - Nov 15 1999

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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title = "Peroxides as oxidative enzyme inhibitors: Mechanism-based inhibition of a cysteine protease by an amino acid ozonide",

abstract = "A stable ozonide derived from Cbz-L-Phe accomplishes rapid and stoichiometric inhibition of papain at less than 100 μM 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.",

author = "Dussault, {Patrick H.} and George, {A. Denise} and Trullinger, {Tony K.}",

note = "Funding Information: Acknowledgments: We are grateful for financial support from the Howard Hughes Medical Institute (ADG) and the NIH and for technical support from Prof. David Berkowitz.",

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T1 - Peroxides as oxidative enzyme inhibitors

T2 - Mechanism-based inhibition of a cysteine protease by an amino acid ozonide

AU - Dussault, Patrick H.

AU - George, A. Denise

AU - Trullinger, Tony K.

N1 - Funding Information: Acknowledgments: We are grateful for financial support from the Howard Hughes Medical Institute (ADG) and the NIH and for technical support from Prof. David Berkowitz.

PY - 1999/11/15

Y1 - 1999/11/15

N2 - A stable ozonide derived from Cbz-L-Phe accomplishes rapid and stoichiometric inhibition of papain at less than 100 μM 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.

AB - A stable ozonide derived from Cbz-L-Phe accomplishes rapid and stoichiometric inhibition of papain at less than 100 μM 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.

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ER -

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

Abstract

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