Syringolin A selectively labels the 20 S proteasome in murine EL4 and wild-type and bortezomib-adapted leukaemic cell lines

Publication

Syringolin A selectively labels the 20 S proteasome in murine EL4 and wild-type and bortezomib-adapted leukaemic cell lines

Journal Paper/Review - Nov 2, 2009

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

Citation

Clerc J, Overkleeft H, Driessen C, Dudler R, Bachmann A, Huber R, Groll M, Kraus M, Florea B, Kaiser M. Syringolin A selectively labels the 20 S proteasome in murine EL4 and wild-type and bortezomib-adapted leukaemic cell lines. Chembiochem : a European journal of chemical biology 2009; 10:2638-43.

Type

Journal Paper/Review (English)

Journal

Chembiochem : a European journal of chemical biology 2009; 10

Publication Date

Nov 2, 2009

Issn Electronic

1439-7633

Pages

2638-43

Brief description/objective

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.