Two Brominated Cyclic Dipeptides Released by the Coldwater Marine Sponge Geodia barretti Act in Synergy As Chemical Defense

Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Center, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
Journal of Natural Products (Impact Factor: 3.8). 02/2011; 74(3):449-54. DOI: 10.1021/np1008812
Source: PubMed


The current work shows that two structurally similar cyclodipeptides, barettin (1) and 8,9-dihydrobarettin (2), produced by the coldwater marine sponge Geodia barretti Bowerbank act in synergy to deter larvae of surface settlers and may also be involved in defense against grazers. Previously, 1 and 2 were demonstrated to bind specifically to serotonergic 5-HT receptors. It may be suggested that chemical defense in G. barretti involves a synergistic action where one of the molecular targets is a 5-HT receptor. A mixture of 1 and 2 lowered the EC(50) of larval settlement as compared to the calculated theoretical additive effect of the two compounds. Moreover, an in situ sampling at 120 m depth using a remotely operated vehicle revealed that the sponge releases these two compounds to the ambient water. Thus, it is suggested that the synergistic action of 1 and 2 may benefit the sponge by reducing the expenditure of continuous production and release of its chemical defense substances. Furthermore, a synergistic action between structurally closely related compounds produced by the same bioenzymatic machinery ought to be the most energy effective for the organism and, thus, is more common than synergy between structurally indistinct compounds.

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    • "Previously, it was shown that these compounds specifically bind to serotonergic 5-HT receptors (Hedner et al., 2006). These findings suggest that the chemical defence in G. barretti involves synergistic action, with congeneric compounds produced by the same enzymatic pathway, where one of the targets is a 5-HT receptor and that the synergy of barettin and 8,9-dihydrobarettin have developed to reduce the cost for the sponge to uphold its chemical defence (Sjögren et al., 2011). "
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    • "Previously, barettin was proven to have anti-fouling properties [4,5,6,7] and these properties are thought to be caused by the serotonin-like structure (Figure 1(1)) [8,9]. The identification of barettin from G. barretti collected outside Northern Norway was the result of the antioxidant screening project at MabCent-SFI [10]. "
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