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A Coumarin‐Labeled Vinyl Sulfone as Tripeptidomimetic Activity‐Based Probe for Cysteine Cathepsins
Author(s) -
Mertens Matthias D.,
Schmitz Janina,
Horn Martin,
Furtmann Norbert,
Bajorath Jürgen,
Mareš Michael,
Gütschow Michael
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201300806
Subject(s) - coumarin , chemistry , cathepsin , cysteine , fluorescence , cathepsin s , cathepsin b , sulfone , recombinant dna , convergent synthesis , combinatorial chemistry , stereochemistry , biochemistry , organic chemistry , enzyme , physics , quantum mechanics , gene
A coumarin‐tetrahydroquinoline hydride 8 was synthesized as a chemical tool for fluorescent labeling. The rigidified tricyclic coumarin structure was chosen for its suitable fluorescence properties. The connection of 8 with a vinyl sulfone building block was accomplished by convergent synthesis thereby leading to the coumarin‐based, tripeptidomimetic activity‐based probe 10 , containing a Gly‐Phe‐Gly motif. Probe 10 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 10 to in‐gel fluorescence imaging.