Details
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 1021-1029 |
| Seitenumfang | 9 |
| Fachzeitschrift | CHEMBIOCHEM |
| Jahrgang | 15 |
| Ausgabenummer | 7 |
| Publikationsstatus | Veröffentlicht - 5 Mai 2014 |
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.
ASJC Scopus Sachgebiete
- Biochemie, Genetik und Molekularbiologie (insg.)
- Biochemie
- Biochemie, Genetik und Molekularbiologie (insg.)
- Molekularmedizin
- Biochemie, Genetik und Molekularbiologie (insg.)
- Molekularbiologie
- Chemie (insg.)
- Organische Chemie
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in: CHEMBIOCHEM, Jahrgang 15, Nr. 7, 05.05.2014, S. 1021-1029.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Baceridin, a cyclic hexapeptide from an epiphytic bacillus strain, inhibits the proteasome
AU - Niggemann, Jutta
AU - Bozko, Przemyslaw
AU - Bruns, Nicole
AU - Wodtke, Anne
AU - Gieseler, Marc Timo
AU - Thomas, Kevin
AU - Jahns, Christine
AU - Nimtz, Manfred
AU - Reupke, Inge
AU - Brüser, Thomas
AU - Auling, Georg
AU - Malek, Nisar
AU - Kalesse, Markus
N1 - Copyright: Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/5/5
Y1 - 2014/5/5
N2 - 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.
AB - 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.
KW - antitumor agents
KW - cyclic peptides
KW - inhibitors
KW - natural products
KW - proteasomes
UR - http://www.scopus.com/inward/record.url?scp=84899635530&partnerID=8YFLogxK
U2 - 10.1002/cbic.201300778
DO - 10.1002/cbic.201300778
M3 - Article
C2 - 24692199
AN - SCOPUS:84899635530
VL - 15
SP - 1021
EP - 1029
JO - CHEMBIOCHEM
JF - CHEMBIOCHEM
SN - 1439-4227
IS - 7
ER -