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Syringolin A Selectively Labels the 20S Proteasome in Murine EL4 and Wild-Type and Bortezomib-Adapted Leukaemic Cell Lines


Clerc, J; Florea, B I; Krauss, M; Groll, M; Huber, R; Bachmann, A S; Dudler, R; Driessen, C; Overkleeft, H S; Kaiser, M (2009). Syringolin A Selectively Labels the 20S Proteasome in Murine EL4 and Wild-Type and Bortezomib-Adapted Leukaemic Cell Lines. ChemBioChem, 10(16):2638-2643.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Plant and Microbial Biology
Dewey Decimal Classification:580 Plants (Botany)
Language:English
Date:2009
Deposited On:18 Nov 2009 10:01
Last Modified:26 Jan 2017 08:45
Publisher:Wiley VCH
ISSN:1439-4227
Additional Information:Free access at Official URL
Publisher DOI:https://doi.org/10.1002/cbic.200900411
Official URL:http://www3.interscience.wiley.com/cgi-bin/fulltext/122595533/PDFSTART

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