Brunsvicamides A−C:  Sponge-Related Cyanobacterial Peptides with Mycobacterium tuberculosis Protein Tyrosine Phosphatase Inhibitory Activity

• Published in: Journal of medicinal chemistry Vol. 49; no. 16; pp. 4871 - 4878
• Main Authors: Müller, Daniela, Krick, Anja, Kehraus, Stefan, Mehner, Christian, Hart, Mark, Küpper, Frithjof C, Saxena, Krishna, Prinz, Heino, Schwalbe, Harald, Janning, Petra, Waldmann, Herbert, König, Gabriele M
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 10-08-2006
• Subjects: Animals; Antibiotics (antibacterial agents, antifungal agents); Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Applied microbiology; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - chemistry; Biological and medical sciences; Cyanobacteria - chemistry; Fundamental and applied biological sciences. Psychology; Microbiology; Molecular Structure; Mycobacterium tuberculosis - enzymology; Peptides, Cyclic - chemistry; Peptides, Cyclic - isolation & purification; Protein Tyrosine Phosphatases - antagonists & inhibitors; Protein Tyrosine Phosphatases - chemistry; Structure-Activity Relationship; Theonella - chemistry; Cyclic peptides; Phosphoric monoester hydrolases; Esterases; Marine environment; Cyanobacteria; Bacteria; Antituberculous agent; Enzyme; Enzyme inhibitor; Animal origin; In vitro; Symbiont; Biological activity; Hexapeptide; Mycobacterium tuberculosis; Microbial origin; Mycobacteriales; Porifera; Mycobacteriaceae; Hydrolases; Isolation; Actinomycetes; Invertebrata; Antibacterial agent; Structural analysis; Protein-tyrosine-phosphatase
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm060327w

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.