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

Rosalina Wisastra, Massimo Ghizzoni, Harm Maarsingh, Adriaan J. Minnaard, Hidde J. Haisma, Frank J. Dekker*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)1817-1822
Number of pages6
JournalOrganic and Biomolecular Chemistry
Volume9
Issue number6
DOIs
Publication statusPublished - 2011

Keywords

  • BIOTINYLATED AFFINITY LABEL
  • NF-KAPPA-B
  • INFLAMMATION

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