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: Daniela Müller, Anja Krick, Stefan Kehraus, Christian Mehner, Mark Hart, Frithjof C Küpper, Krishna Saxena, Heino Prinz, Harald Schwalbe, Petra Janning, Herbert Waldmann, Gabriele M König
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 49 Issue 16 Pg. 4871-8 (Aug 10 2006) ISSN: 0022-2623 [Print] United States
• PMID: 16884299 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• MptpA protein, Mycobacterium tuberculosis
• Peptides, Cyclic
• brunsvicamide A
• brunsvicamide B
• brunsvicamide C
• Protein Tyrosine Phosphatases

Topics

• Animals
• Bacterial Proteins (antagonists & inhibitors, chemistry)
• Cyanobacteria (chemistry)
• Molecular Structure
• Mycobacterium tuberculosis (enzymology)
• Peptides, Cyclic (chemistry, isolation & purification)
• Protein Tyrosine Phosphatases (antagonists & inhibitors, chemistry)
• Structure-Activity Relationship
• Theonella (chemistry)