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

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

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

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 20S 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.

Original languageEnglish
Pages (from-to)2638-2643
Number of pages6
JournalChemBioChem
Volume10
Issue number16
DOIs
StatePublished - 2 Nov 2009

Keywords

  • Antitumor agents
  • Leukemia
  • Natural products
  • Proteasome inhibitors
  • Syrbactin

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