Antifouling Activity of Brominated Cyclopeptides from the Marine Sponge Geodia barretti

• Published in: Journal of natural products (Washington, D.C.) Vol. 67; no. 3; pp. 368 - 372
• Main Authors: Sjögren, Martin, Göransson, Ulf, Johnson, Ann-Louise, Dahlström, Mia, Andersson, Rolf, Bergman, Jan, Jonsson, Per R, Bohlin, Lars
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 2004; Glendale, AZ American Society of Pharmacognosy
• Subjects: ACANTHELLA-CAVERNOSA; Aminoacids, peptides. Hormones. Neuropeptides; ANALOGS; Analytical, structural and metabolic biochemistry; Animals; Balanus improvisus; BALANUS-AMPHITRITE; BARETTIN; BARNACLE LARVAE; Biological and medical sciences; Cirripedia; Demospongiae; DERIVATIVES; Dose-Response Relationship, Drug; Ecology; Ekologi; FARMACI; Fundamental and applied biological sciences. Psychology; Geodia barretti; INVERTEBRATE; Larva - drug effects; Marine; Marine Biology; Medicin och hälsovetenskap; METABOLITES; Molecular Structure; NATURAL SCIENCES; NATURVETENSKAP; Oceans and Seas; PEPTIDES; Peptides, Cyclic - chemistry; Peptides, Cyclic - isolation & purification; Peptides, Cyclic - pharmacology; PHARMACY; Porifera - chemistry; Proteins; SETTLEMENT; Stereoisomerism; Thoracica - drug effects; Molecular rigidity; Peptides; Nitrogen heterocycle; Animal origin; Biological activity; Crustacea; Marine environment; Larva; Structure activity relation; Porifera; Arthropoda; Six membered ring; Antifouling protection; Concentration effect; Bicyclic compound; Dipeptides; Cirripedia; Balanus; Isolation; Bromine Organic compounds; Aromatic compound; Fluorine Organic compounds; Invertebrata; Structural analysis
• ISSN: 0163-3864; 1520-6025; 1520-6025
• DOI: 10.1021/np0302403

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 Balanus improvisus, 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 EC50 values of 0.9 and 7.9 μM, 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 μM. 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.