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.
MeSH terms
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Cathepsin B / antagonists & inhibitors*
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Inhibitory Concentration 50
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Kinetics
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Models, Molecular
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Molecular Structure
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / pharmacology
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Sulfhydryl Compounds / chemistry*
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Thiazoles / chemical synthesis*
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Thiazoles / pharmacology
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p300-CBP Transcription Factors / antagonists & inhibitors*
Substances
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Enzyme Inhibitors
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Protease Inhibitors
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Sulfhydryl Compounds
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Thiazoles
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isothiazolidinone
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p300-CBP Transcription Factors
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p300-CBP-associated factor
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Cathepsin B