title: Brunsvicamides A-C: sponge-related cyanobacterial peptides with Mycobacterium tuberculosis protein tyrosine phosphatase inhibitory activity.
abstract: The cyanobacterium Tychonema sp. produces the new cyclic hexapeptides brunsvicamide A-C (1-3). Brunsvicamide B (2) and C (3) selectively inhibit the Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB), a potential drug target for tuberculosis therapy for which no inhibitors are known to date. Brunsvicamide C contains an N-methylated N'-formylkynurenine moiety, a unique structural motif in cyclic peptides. The new peptides are related to the sponge-derived mozamides, supporting the suggestion that secondary metabolites of certain marine invertebrates are produced by associated microorganisms. Thus, microorganisms phylogenetically related to symbionts of marine invertebrates can be judged as a means to supply "marine-like" compounds for drug development.
authors.affiliation: Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Müller
authors.forename: Anja
authors.initials: A
authors.lastname: Krick
authors.forename: Stefan
authors.initials: S
authors.lastname: Kehraus
authors.forename: Christian
authors.initials: C
authors.lastname: Mehner
authors.forename: Mark
authors.initials: M
authors.lastname: Hart
authors.forename: Frithjof C
authors.initials: FC
authors.lastname: Küpper
authors.forename: Krishna
authors.initials: K
authors.lastname: Saxena
authors.forename: Heino
authors.initials: H
authors.lastname: Prinz
authors.forename: Harald
authors.initials: H
authors.lastname: Schwalbe
authors.forename: Petra
authors.initials: P
authors.lastname: Janning
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: König
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D000458:Cyanobacteria / Q000737:chemistry*; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000302:isolation & purification; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013329:Structure-Activity Relationship; D047232:Theonella / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; C414465:MptpA protein, Mycobacterium tuberculosis; D010456:Peptides, Cyclic; C513364:brunsvicamide A; C513365:brunsvicamide B; C513366:brunsvicamide C; D017027:Protein Tyrosine Phosphatases