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Antifouling Activity of Brominated Cyclopeptides from the Marine Sponge Geodia barretti
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
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2004 (English)In: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 67, no 3, 368-372 p.Article in journal (Refereed) Published
Abstract [en]

In this work, we show the potent antifouling effects of two compounds, barettin (cyclo[(6-bromo-8-entryptophan)arginine]) (1), isolated as a Z/E mixture (87/13), and 8,9-dihydrobarettin (cyclo[(6-bromotryptophan)arginine]) (2), isolated from the marine sponge Geodia barretti. The compounds were isolated guided by their ability to inhibit the settlement of cyprid larvae of the barnacle Balanusimprovisus, and their structures were determined by means of mass spectrometry, NMR, and quantitative amino acid analysis. The activities of these brominated diketopiperazine-like cyclic dipeptides are in the range of antifouling agents in use today, as shown by their EC(50) values of 0.9 and 7.9 microM, respectively. However, contrary to today's antifouling agents, the effects of barettin and 8,9-dihydrobarettin are nontoxic and reversible. A small set of synthetic analogues, including l-arginine, l-tryptophan, 5-bromo-d,l-tryptophan, 6-bromo-d,l-tryptophan, and 6-fluoro-d,l-tryptophan, were tested for possible structure-activity relationships. None of these compounds showed any effect at a concentration of 10 microM. We hypothesize that the isolated compounds are part of the sponge's chemical defense to deter fouling organisms. This theory is supported by the fact that barettin is found in water exposed to living specimens of G. barretti in concentrations that completely inhibit barnacles from settling.

Place, publisher, year, edition, pages
2004. Vol. 67, no 3, 368-372 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-94324DOI: 10.1021/np0302403PubMedID: 15043412OAI: oai:DiVA.org:uu-94324DiVA: diva2:168138
Available from: 2006-04-19 Created: 2006-04-19 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Bioactive Compounds from the Marine Sponge Geodia barretti: Characterization, Antifouling Activity and Molecular Targets
Open this publication in new window or tab >>Bioactive Compounds from the Marine Sponge Geodia barretti: Characterization, Antifouling Activity and Molecular Targets
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The marine sponge Geodia barretti produces a range of secondary metabolites. Two of these compounds were isolated and elucidated guided by their ability to inhibit settlement of cypris larvae of the barnacle Balanus improvisus. The compounds barettin (cyclo-[(6-bromo-8-en-tryptophan)-arginine]) as E/Z mixture and 8,9-dihydrobarettin (cyclo-[6-bromo-tryptophan)-arginine]) were determined by using mass spectrometry, nuclear magnetic resonance and quantitative amino acid analysis.The bioactivity of these brominated dipeptides is in the range of antifouling substances used today: EC50 values of 0.9 µM (barettin) and 7.9 µM (8,9-dihydrobarettin). The compounds were successfully synthesised and then tested in a field experiment to evaluate their antifouling properties. The compounds were incorporated in four different commerical, non-toxic marine coatings. The concentrations of the compounds were 0.1 and 0.01% (w/w) and coated panels were exposed to field conditions for eight weeks. The experiment evaluated the effect of barettin and 8,9-dihydrobarettin on recruitment of the barnacle B. improvisus and the blue mussel Mytilus edulis (major Swedish foulers). The most efficient paint was a SPC polymer, for which the reduction of recruitment of B. improvisus was 89% with barettin (0.1%) and 61% with 8,9-dihydrobarettin (0.1%). For M. edulis the reduction of recruitment was 81% with barettin (0.1%) and 72% with 8,9-dihydrobarettin (0.1%) with the same SPC paint. Furthermore, 14 analogs of barettin and dipodazine were synthesised and tested for their ability to inhibit larval settlement. Two of the analogs have a barettin scaffold and twelve have a dipodazine scaffold. Six of the analogs displayed significant settlement inhibition with the most potent inhibitor being benzo[g]dipodazine (EC50 value 0.034 µM). The effect of benzo[g]dipodazine was also shown to be reversible. Finally, an investigation of the mode of action was performed on 5-HT receptors. Barettin demonstrated a specific affinity to 5-HT2A, 5-HT2C and 5-HT4, while 8,9-dihydrobarettin interacted only with 5-HT2C of the receptor subtypes tested (5-HT1-5-HT7).

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 57 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 32
Keyword
Pharmacognosy, Geodia barretti, barettin, secondary metabolites, settling inhibition, Balanus improvisus, analogs, 5-HT, Farmakognosi
Identifiers
urn:nbn:se:uu:diva-6797 (URN)91-554-6534-X (ISBN)
Public defence
2006-05-11, C10:305, BMC, Box 574, 75123, Uppsala, 09:30
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Supervisors
Available from: 2006-04-19 Created: 2006-04-19Bibliographically approved

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