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

被引：57

作者：

Clerc, Jerome ^{[1
]}

Florea, Bogdan I. ^{[2
,3
]}

Kraus, Marianne ^{[4
]}

Groll, Michael ^{[5
]}

Huber, Robert ^{[6
,7
,8
]}

Bachmann, Andre S. ^{[9
]}

Dudler, Robert ^{[10
]}

Driessen, Christoph ^{[4
]}

Overkleeft, Herman S. ^{[2
,3
]}

Kaiser, Markus ^{[1
]}

机构：

[1] Max Planck Gesell, Chem Genom Ctr, D-44227 Dortmund, Germany

[2] Leiden Inst Chem, NL-2333 CC Leiden, Netherlands

[3] Netherlands Prote Ctr, Gorlaeus Labs, NL-2333 CC Leiden, Netherlands

[4] Cantonal Hosp St Gallen, Expt Oncol Lab, CH-9007 St Gallen, Switzerland

[5] Tech Univ Munich, Ctr Integrated Prot Sci, Dept Chem, D-85747 Garching, Germany

[6] Max Planck Inst Biochem, D-82152 Martinsried, Germany

[7] Univ Duisburg Essen, Zentrum Med Biotechnol, D-45117 Essen, Germany

[8] Cardiff Univ, Sch Biosci, Cardiff CF10 3US, S Glam, Wales

[9] Univ Hawaii Manoa, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA

[10] Univ Zurich, Inst Plant Biol, Zurich Basel Plant Sci Ctr, CH-8008 Zurich, Switzerland

来源：

CHEMBIOCHEM | 2009年 / 10卷 / 16期

基金：

瑞士国家科学基金会;

关键词：

antitumor agents; leukemia; natural products; proteasome inhibitors; syrbactin; ACTIVITY-BASED PROBES; IN-VIVO; INHIBITOR BORTEZOMIB; TMC-95A ANALOGS; YEAST; PROTEIN; SPECIFICITY; RESISTANCE; MECHANISM; BACTERIUM;

D O I：

10.1002/cbic.200900411

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The natural product syringolin A (SyIA) 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.

引用

页码：2638 / 2643

页数：6

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