title: Antifouling activity of brominated cyclopeptides from the marine sponge Geodia barretti.
abstract: 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.
authors.affiliation: Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, PO Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Sjögren
authors.forename: Ulf
authors.initials: U
authors.lastname: Göransson
authors.forename: Ann-Louise
authors.initials: AL
authors.lastname: Johnson
authors.forename: Mia
authors.initials: M
authors.lastname: Dahlström
authors.forename: Rolf
authors.initials: R
authors.lastname: Andersson
authors.forename: Jan
authors.initials: J
authors.lastname: Bergman
authors.forename: Per R
authors.initials: PR
authors.lastname: Jonsson
authors.forename: Lars
authors.initials: L
authors.lastname: Bohlin
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007814:Larva / Q000187:drug effects; D008386:Marine Biology; D015394:Molecular Structure; D009792:Oceans and Seas; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism; D001468:Thoracica / Q000187:drug effects
chemical_list: C484473:8,9-dihydrobarettin; D010456:Peptides, Cyclic; C484472:barettin