Clerc, Jérôme; Schellenberg, Barbara; Groll, Michael; Bachmann, André S.; Huber, Robert; Dudler, Robert; Kaiser, Markus:
Convergent Synthesis and Biological Evaluation of Syringolin A and Derivatives as Eukaryotic 20S Proteasome Inhibitors
2010
In: European journal of organic chemistry : EurJOC, Heft 21, S. 3991 - 4003
Artikel/Aufsatz in Zeitschrift2010Biologie
Fakultät für Biologie
Titel:
Convergent Synthesis and Biological Evaluation of Syringolin A and Derivatives as Eukaryotic 20S Proteasome Inhibitors
Autor(in):
Clerc, Jérôme; Schellenberg, Barbara; Groll, Michael; Bachmann, André S.; Huber, RobertLSF; Dudler, Robert; Kaiser, MarkusLSF
Erscheinungsjahr
2010
WWW URL

Abstract:

A convergent synthesis of SylA was developed and consists of the synthesis of a fully functionalized macrocycle, which is subsequently coupled with a urea moiety. For cyclization, ring-closing metathesis of a conformationally preorganized precursor was employed. The established synthetic route was then applied to the synthesis of SylA derivatives by using various peptidic side chains for decoration of the SylA macrocycle. The resulting collection of SylA analogues was tested for proteasome inhibition, revealing PEGylated SylA derivatives as the most potent proteasome inhibitors.