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Syringolin A Selectively Labels the 20 S Proteasome in Murine EL4 and Wild‐Type and Bortezomib‐Adapted Leukaemic Cell Lines
Author(s) -
Clerc Jérôme,
Florea Bogdan I.,
Kraus Marianne,
Groll Michael,
Huber Robert,
Bachmann André S.,
Dudler Robert,
Driessen Christoph,
Overkleeft Herman S.,
Kaiser Markus
Publication year - 2009
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.200900411
Subject(s) - bortezomib , proteasome , cell culture , proteasome inhibitor , chemistry , natural product , small molecule , cell , biology , cancer research , biochemistry , immunology , multiple myeloma , genetics
The natural product syringolin A (SylA) is a potent proteasome inhibitor with promising anticancer activities. To further investigate its potential as a lead structure, selectivity profiling with cell lysates was performed. At therapeutic concentrations, a rhodamine‐tagged SylA derivative selectively bound to the 20 S proteasome active sites without detectable off‐target labelling. Additional profiling with lysates of wild‐type and bortezomib‐adapted leukaemic cell lines demonstrated the retention of this proteasome target and subsite selectivity as well as potency even in clinically relevant cell lines. Our studies, therefore, propose that further development of SylA might indeed result in an improved small molecule for the treatment of leukaemia.