A cell-permeable inhibitor and activity-based probe for the caspase-like activity of the proteasome

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 12; pp. 3402 - 3405
• Main Authors: van Swieten, Paul F., Samuel, Emlyn, Hernández, Rosa Orient, van den Nieuwendijk, Adrianus M.C.H., Leeuwenburgh, Michiel A., van der Marel, Gijsbert A., Kessler, Benedikt M., Overkleeft, Herman S., Kisselev, Alexei F.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.06.2007; Elsevier
• Subjects: Antigen presentation; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Azide; Azides - chemistry; Binding Sites; Biological and medical sciences; Caspases - chemistry; Caspases - metabolism; Cell Membrane Permeability - drug effects; Cell Membrane Permeability - physiology; Cysteine Proteinase Inhibitors - chemical synthesis; Cysteine Proteinase Inhibitors - pharmacology; General aspects; Humans; Medical sciences; Models, Chemical; Pharmacology. Drug treatments; Protease inhibitor; Proteasome; Proteasome Endopeptidase Complex - chemistry; Proteasome Endopeptidase Complex - immunology; Proteasome Inhibitors; Ubiquitin; Ubiquitin; Antigen presentation; Azide; Protease inhibitor; Proteasome; Multicatalytic endopeptidase complex; Peptides; Sulfone; Cysteine endopeptidases; Active site; Tripeptide; Selectivity; Subunit; Functionalization; Vinylic compound; Chemical synthesis; Serine endopeptidases; Enzyme; Organic azide; Caspase; Enzyme inhibitor; Biological activity; Protein; Peptidases; Vertebrata; Trypsin; Mammalia; Phenols; Hydrolases

A subunit-specific proteasome inhibitor was developed and its specificity was assayed both by fluorescent substrate hydrolysis and by visualization of the targeted subunits via an activity-based probe approach. The ubiquitin–proteasome pathway degrades the majority of proteins in mammalian cells and...