title: Antifouling bastadin congeners target mussel phenoloxidase and complex copper(II) ions.
abstract: Synthetically prepared congeners of sponge-derived bastadin derivatives such as 5,5'-dibromohemibastadin-1 (DBHB) that suppress the settling of barnacle larvae were identified in this study as strong inhibitors of blue mussel phenoloxidase that is involved in the firm attachment of mussels to a given substrate. The IC₅₀ value of DBHB as the most active enzyme inhibitor encountered in this study amounts to 0.84 μM. Inhibition of phenoloxidase by DBHB is likely due to complexation of copper(II) ions from the catalytic centre of the enzyme by the α-oxo-oxime moiety of the compound as shown here for the first time by structure activity studies and by X-ray structure determination of a copper(II) complex of DBHB.
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors.forename: Mirko
authors.initials: M
authors.lastname: Bayer
authors.forename: Claire
authors.initials: C
authors.lastname: Hellio
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Maréchal
authors.forename: Walter
authors.initials: W
authors.lastname: Frank
authors.forename: Wenhan
authors.initials: W
authors.lastname: Lin
authors.forename: Horst
authors.initials: H
authors.lastname: Weber
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
mesh_terms: D000818:Animals; D049872:Bivalvia / Q000187:drug effects / Q000201:enzymology*; D002498:Centrifugation; D045424:Complex Mixtures / Q000032:analysis*; D003300:Copper / Q000378:metabolism*; D003460:Crystallization; D018360:Crystallography, X-Ray; D055768:Halogenated Diphenyl Ethers / Q000032:analysis / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D011161:Porifera / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D045424:Complex Mixtures; D055768:Halogenated Diphenyl Ethers; D003300:Copper; D014442:Monophenol Monooxygenase