title: Baceridin, a cyclic hexapeptide from an epiphytic bacillus strain, inhibits the proteasome.
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.
authors.affiliation: Helmholtz Centre for Infection Research (HZI), Inhoffenstrasse 7, 38124 Braunschweig (Germany).
authors.forename: Jutta
authors.initials: J
authors.lastname: Niggemann
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Bozko
authors.forename: Nicole
authors.initials: N
authors.lastname: Bruns
authors.forename: Anne
authors.initials: A
authors.lastname: Wodtke
authors.forename: Marc Timo
authors.initials: MT
authors.lastname: Gieseler
authors.forename: Kevin
authors.initials: K
authors.lastname: Thomas
authors.forename: Christine
authors.initials: C
authors.lastname: Jahns
authors.forename: Manfred
authors.initials: M
authors.lastname: Nimtz
authors.forename: Inge
authors.initials: I
authors.lastname: Reupke
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüser
authors.forename: Georg
authors.initials: G
authors.lastname: Auling
authors.forename: Nisar
authors.initials: N
authors.lastname: Malek
authors.forename: Markus
authors.initials: M
authors.lastname: Kalesse
mesh_terms: D017209:Apoptosis; D001407:Bacillus / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D007536:Isomerism; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D010456:Peptides, Cyclic; D016159:Tumor Suppressor Protein p53; C000594503:baceridin; D046988:Proteasome Endopeptidase Complex
keywords: antitumor agents; cyclic peptides; inhibitors; natural products; proteasomes