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Omuralide and Vibralactone: Differences in the Proteasome‐ β‐Lactone‐γ‐Lactam Binding Scaffold Alter Target Preferences |
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| Authors: | Dr. Nerea Gallastegui Marion Rusch Dr. Christian Hedberg Prof. Dr. Stephan A. Sieber Prof. Dr. Michael Groll |
| Affiliation: | 1. Center for Integrated Protein Science Munich, Department Chemie, Technische Universit?t München, Lichtenbergstrasse 4, 85747 Garching (Germany);2. Max Planck Institute of Molecular Physiology, Otto Hahn Strasse 11, 44227 Dortmund (Germany);3. Center for Integrated Protein Science Munich, Department Chemie, Lehrstuhl für Organische Chemie II, Technische Universit?t München, Lichtenbergstrasse 4, Garching, 85747 (Germany) |
| Abstract: | Despite their structural similarity, the natural products omuralide and vibralactone have different biological targets. While omuralide blocks the chymotryptic activity of the proteasome with an IC50 value of 47 nM, vibralactone does not have any effect at this protease up to a concentration of 1 mM . Activity‐based protein profiling in HeLa cells revealed that the major targets of vibralactone are APT1 and APT2. |
| Keywords: | click chemistry drug development natural products proteasome protein crystallography |