title: Intramolecular modulation of serine protease inhibitor activity in a marine cyanobacterium with antifeedant properties.
abstract: Extracts of the Floridian marine cyanobacterium Lyngbya cf. confervoides were found to deter feeding by reef fish and sea urchins (Diadema antillarum). This antifeedant activity may be a reflection of the secondary metabolite content, known to be comprised of many serine protease inhibitors. Further chemical and NMR spectroscopic investigation led us to isolate and structurally characterize a new serine protease inhibitor 1 that is formally derived from an intramolecular condensation of largamide D (2). The cyclization resulted in diminished activity, but to different extents against two serine proteases tested. This finding suggests that cyanobacteria can endogenously modulate the activity of their protease inhibitors.
authors.affiliation: Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA. susmatt@ufl.edu
authors.forename: Susan
authors.initials: S
authors.lastname: Matthew
authors.forename: Ranjala
authors.initials: R
authors.lastname: Ratnayake
authors.forename: Mikel A
authors.initials: MA
authors.lastname: Becerro
authors.forename: Raphael
authors.initials: R
authors.lastname: Ritson-Williams
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Paul
authors.forename: Hendrik
authors.initials: H
authors.lastname: Luesch
mesh_terms: D000818:Animals; D001267:Atlantic Ocean; D001427:Bacterial Toxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D000458:Cyanobacteria / Q000302:isolation & purification / Q000378:metabolism*; D047630:Depsipeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D005399:Fishes; D005431:Florida; D008387:Marine Toxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009994:Osmolar Concentration; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D012617:Sea Urchins; D012623:Seawater / Q000382:microbiology; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D001427:Bacterial Toxins; D047630:Depsipeptides; D008387:Marine Toxins; D015842:Serine Proteinase Inhibitors; C555914:largamide D; D002918:Chymotrypsin; D010196:Pancreatic Elastase