Clerc, Jérôme; Florea, Bogdan I.; Kraus, Marianne; Groll, Michael; Huber, Robert; Bachmann, André S.; Dudler, Robert; Driessen, Christoph; Overkleeft, Herman S.; Kaiser, Markus:

Syringolin A selectively labels the 20S proteasome in murine EL4 and wildtype and bortezomib adapted leukemic cell lines

In: ChemBioChem : a European journal of chemical biology, Jg. 10 (2009) ; Nr. 16, S. 2638-2643
ISSN: 1439-4227
Zeitschriftenaufsatz / Fach: Biologie
Fakultät für Biologie
Abstract:
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.