Brunsvicamide A-C, sponge-related cyanobacterial peptides with Mycobacterium tuberculosis protein tyrosine phosphatase inhibitory activity

Daniela Müller, Anja Krick, S Kehraus, Mark Hart, Frithjof Küpper, Heino Prinz, P Janning, Herbert Waldmann, Harald Schwalbe, Krishna Saxena, Gabriele Maria König

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Abstract

Non-methane hydrocarbons (NMHCs) are produced naturally in the ocean and by terrestrial vegetation. Owing to its high reactivity and flux, isoprene (2-methyl-1,3-butadiene) is important in controlling the balance of atmospheric oxidants, and altering air quality on both local and global scales. Here we show, for the first time, that macroalgae (seaweeds) emit isoprene and a number of other non-methane hydrocarbons (NMHCs). We observed NMHC concentrations in rockpools containing macroalgae and estimated fluxes to the atmosphere over a full diurnal cycle. Emissions at our temperate coastal site (Mace Head, Ireland) in autumn are intermediate in magnitude between terrestrial and ocean fluxes (on a unit area basis), and may contribute significant concentrations to the local atmosphere. We also carried out a series of controlled laboratory experiments focusing on isoprene, in natural and artificial light, and under different temperature conditions involving red (Chondrus crispus, Asparagopsis armata), green (Ulva intestinalis, formerly known as Enteromorpha intestinalis) and brown (Laminaria digitata, Ascophyllum nodosum, Pelvetia canaliculata, Fucus vesiculosus, Fucus serratus, Halidrys siliquosa and Laminaria saccharina) macroalgae commonly found on the west coast of Ireland. We observed NMHC emissions from all the algae investigated and emissions were dominated by alkenes. Production is species-dependent, temperature-dependent and related to light availability. We discuss our observations in the context of what is known about the production of isoprene and ethene in higher plants. (C) 2004 Elsevier B.V. All rights reserved.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.
Original languageEnglish
Pages (from-to)4871-4878
Number of pages8
JournalJ MED CHEM
Volume49
Issue number16
DOIs
Publication statusPublished - 2006

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Keywords

  • VHR
  • MARINE-ALGAE
  • ETHYLENE-BIOSYNTHESIS
  • ERK
  • PATHWAY
  • ATLANTICMONODONTA-LABIO LINNE
  • CYCLIC HEXAPEPTIDES
  • SURFACE SEAWATER
  • TRACE GASES
  • PHOTOSYNTHESIS
  • Chemistry, Multidisciplinary
  • OceanographyChemistry, Medicinal
  • EMISSION
  • ALKALOIDS
  • THEONELLA SP
  • SPECIFICITY
  • VOLATILE ORGANIC-COMPOUNDS
  • MACE HEAD
  • PLANTS

Cite this

Müller, D., Krick, A., Kehraus, S., Hart, M., Küpper, F., Prinz, H., Janning, P., Waldmann, H., Schwalbe, H., Saxena, K., & König, G. M. (2006). Brunsvicamide A-C, sponge-related cyanobacterial peptides with Mycobacterium tuberculosis protein tyrosine phosphatase inhibitory activity. J MED CHEM, 49(16), 4871-4878. https://doi.org/10.1021/jm060327w