title: Two brominated cyclic dipeptides released by the coldwater marine sponge Geodia barretti act in synergy as chemical defense.
abstract: 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.
authors.affiliation: Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Center, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Sjögren
authors.forename: Per R
authors.initials: PR
authors.lastname: Jonsson
authors.forename: Mia
authors.initials: M
authors.lastname: Dahlström
authors.forename: Tomas
authors.initials: T
authors.lastname: Lundälv
authors.forename: Robert
authors.initials: R
authors.lastname: Burman
authors.forename: Ulf
authors.initials: U
authors.lastname: Göransson
authors.forename: Lars
authors.initials: L
authors.lastname: Bohlin
mesh_terms: D000818:Animals; D033381:Anomura / Q000187:drug effects; D003080:Cold Temperature; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification*; D047231:Geodia / Q000737:chemistry*; D006842:Hydrocarbons, Brominated / Q000737:chemistry / Q000302:isolation & purification*; D007814:Larva / Q000187:drug effects; D008386:Marine Biology; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification*; D011985:Receptors, Serotonin / Q000187:drug effects; D001468:Thoracica / Q000187:drug effects; D014867:Water
chemical_list: C484473:8,9-dihydrobarettin; D047630:Depsipeptides; D006842:Hydrocarbons, Brominated; D010456:Peptides, Cyclic; D011985:Receptors, Serotonin; C484472:barettin; D014867:Water