Baceridin, a cyclic hexapeptide from an epiphytic bacillus strain, inhibits the proteasome
- verfasst von
- Jutta Niggemann, Przemyslaw Bozko, Nicole Bruns, Anne Wodtke, Marc Timo Gieseler, Kevin Thomas, Christine Jahns, Manfred Nimtz, Inge Reupke, Thomas Brüser, Georg Auling, Nisar Malek, Markus Kalesse
- Abstract
A new cyclic hexapeptide, baceridin (1), was isolated from the culture medium of a plant-associated Bacillus strain. The structure of 1 was elucidated by HR-HPLC-MS and 1D and 2D NMR experiments and confirmed by ESI MS/MS sequence analysis of the corresponding linear hexapeptide 2. The absolute configurations of the amino acid residues were determined after derivatization by GC-MS and Marfey's method. The cyclopeptide 1 consists partially of nonribosomal-derived D- and allo-D-configured amino acids. The order of the D- and L-leucine residues within the sequence cyclo(-L-Trp-D-Ala-D-allo-Ile-L-Val-D-Leu-L-Leu-) was assigned by total synthesis of the two possible stereoisomers. Baceridin (1) was tested for antimicrobial and cytotoxic activity and displayed moderate cytotoxicity (1-2 μg-‰mL-1) as well as weak activity against Staphylococcus aureus. However, it was identified to be a proteasome inhibitor that inhibits cell cycle progression and induces apoptosis in tumor cells by a p53-independent pathway. Go your own way: The cyclic hexapeptide baceridin was isolated from the culture medium of a plant-associated Bacillus strain. The configuration could be assigned by chemical degradation and total synthesis. In the course of biological validations baceridin was identified as a proteasome inhibitor that inhibits cell-cycle progression and induces apoptosis in tumor cells by a p53-independent pathway.
- Organisationseinheit(en)
-
Institut für Mikrobiologie
Institut für Organische Chemie
- Externe Organisation(en)
-
Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
Eberhard Karls Universität Tübingen
- Typ
- Artikel
- Journal
- CHEMBIOCHEM
- Band
- 15
- Seiten
- 1021-1029
- Anzahl der Seiten
- 9
- ISSN
- 1439-4227
- Publikationsdatum
- 05.05.2014
- Publikationsstatus
- Veröffentlicht
- Peer-reviewed
- Ja
- ASJC Scopus Sachgebiete
- Biochemie, Molekularmedizin, Molekularbiologie, Organische Chemie
- Elektronische Version(en)
-
https://doi.org/10.1002/cbic.201300778 (Zugang:
Geschlossen)