Brunsvicamides A-C: sponge-related cyanobacterial peptides with Mycobacterium tuberculosis protein tyrosine phosphatase inhibitory activity.
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.
Müller
Daniela
D
Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany.
Krick
Anja
A
Kehraus
Stefan
S
Mehner
Christian
C
Hart
Mark
M
Küpper
Frithjof C
FC
Saxena
Krishna
K
Prinz
Heino
H
Schwalbe
Harald
H
Janning
Petra
P
Waldmann
Herbert
H
König
Gabriele M
GM
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
D001426:Bacterial Proteins; C414465:MptpA protein, Mycobacterium tuberculosis; D010456:Peptides, Cyclic; C513364:brunsvicamide A; C513365:brunsvicamide B; C513366:brunsvicamide C; D017027:Protein Tyrosine Phosphatases