A Coumarin‐Labeled Vinyl Sulfone as Tripeptidomimetic Activity‐Based Probe for Cysteine Cathepsins. Issue 7 (19th March 2014)

• Record Type: Journal Article
• Authors: Mertens, Matthias D.; Schmitz, Janina; Horn, Martin; Furtmann, Norbert; Bajorath, Jürgen; Mareš, Michael; Gütschow, Michael
• Is Part Of: Chembiochem. Volume 15:Issue 7(2014)
• Page Start: 955
• Page End: 959
• Publication Date: 2014-03-19
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201300806
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A coumarin‐tetrahydroquinoline hydride <bold>8</bold> was synthesized as a chemical tool for fluorescent labeling. The rigidified tricyclic coumarin structure was chosen for its suitable fluorescence properties. The connection of <bold>8</bold> with a vinyl sulfone building block was accomplished by convergent synthesis thereby leading to the coumarin‐based, tripeptidomimetic activity‐based probe <bold>10</bold>, containing a Gly‐Phe‐Gly motif. Probe <bold>10</bold> was evaluated as inactivator of the therapeutically relevant human cysteine cathepsins S, L, K, and B: it showed particularly strong inactivation of cathepsin S. The detection of recombinant and native cathepsin S was demonstrated by applying <bold>10</bold> to in‐gel fluorescence imaging.</p> </abstract>