Issue 6, 2011
From the journal:

Organic & Biomolecular Chemistry

Isothiazolones; thiol-reactive inhibitors of cysteine protease cathepsin B and histone acetyltransferase PCAF†

Rosalina Wisastra,a   Massimo Ghizzoni,a   Harm Maarsingh,b   Adriaan J. Minnaard,c   Hidde J. Haismaa  and  Frank J. Dekker*a  

* Corresponding authors

a Department of Pharmaceutical Gene Modulation, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen, The Netherlands
E-mail: f.j.dekker@rug.nl

b Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen, The Netherlands

c Department of Bio-organic Chemistry, Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, Groningen, The Netherlands

Abstract

Isothiazolones and 5-chloroisothiazolones react chemoselectively with thiols by cleavage of the weak nitrogen–sulfur bond to form disulfides. They show selectivity for inhibition of the thiol-dependent cysteine protease cathepsin B and the histone acetyltransferase p300/CBP associated factor (PCAF) based on their substitution pattern. Furthermore, enzyme kinetics and mass spectroscopy indicate covalent binding of a 5-chloroisothiazolone to cathepsin B, which demonstrates their potential utility as probes for activity-based protein profiling.

Graphical abstract: Isothiazolones; thiol-reactive inhibitors of cysteine protease cathepsin B and histone acetyltransferase PCAF

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Article information

DOI
https://doi.org/10.1039/C0OB00464B
Article type
Paper
Submitted
21 Jul 2010
Accepted
08 Dec 2010
First published
25 Jan 2011

Org. Biomol. Chem., 2011,9, 1817-1822

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Isothiazolones; thiol-reactive inhibitors of cysteine protease cathepsin B and histone acetyltransferase PCAF

R. Wisastra, M. Ghizzoni, H. Maarsingh, A. J. Minnaard, H. J. Haisma and F. J. Dekker, Org. Biomol. Chem., 2011, 9, 1817 DOI: 10.1039/C0OB00464B

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