Antibiotics from Gliding Bacteria, Part 100; for Part 99, see: B. Kunze, R. Jansen, G. Höfle, H. Reichenbach, J. Antibiot.2004, 57, 151–155. We thank I. Schleicher, K. Schober, S. Reinecke, A. Ritter, and B. Hinkelmann for technical assistance, Dr. A. Ross and colleagues at the bio-pilotplant of the GBF for help with fermentations, Dr. V. Wray and colleagues for recording NMR and mass spectra, and Dr. H.-J. Hecht for generating stereopictures. We also thank Prof. G. R. Pettit for a generous gift of dolastatin 10. This work was supported by Morphochem AG and the Fonds der Chemischen Industrie.
Isolation, Crystal and Solution Structure Determination, and Biosynthesis of Tubulysins—Powerful Inhibitors of Tubulin Polymerization from Myxobacteria†
Article first published online: 16 SEP 2004
Copyright © 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 43, Issue 37, pages 4888–4892, September 20, 2004
How to Cite
Steinmetz, H., Glaser, N., Herdtweck, E., Sasse, F., Reichenbach, H. and Höfle, G. (2004), Isolation, Crystal and Solution Structure Determination, and Biosynthesis of Tubulysins—Powerful Inhibitors of Tubulin Polymerization from Myxobacteria. Angew. Chem. Int. Ed., 43: 4888–4892. doi: 10.1002/anie.200460147
- Issue published online: 16 SEP 2004
- Article first published online: 16 SEP 2004
- Manuscript Received: 29 MAR 2004
- antitumor agents;
- natural products;
- structure elucidation
Myxobacteria have it both ways: Whereas the epothilones stabilize the tubulin cytoskeleton and build microtubuli, tubulysins, which have now been isolated from Archangium gephyra and Angiococcus disciformis, have exactly the opposite effect. They induce the disintegration of the microtubuli, and even picomolar concentrations can cause cell death by apoptosis. Their effect on cell cultures exceeds that of the most active epothilones by 50-fold.