Intramolecular modulation of serine protease inhibitor activity in a marine cyanobacterium with antifeedant properties.
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.
Matthew
Susan
S
Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA. susmatt@ufl.edu
Ratnayake
Ranjala
R
Becerro
Mikel A
MA
Ritson-Williams
Raphael
R
Paul
Valerie J
VJ
Luesch
Hendrik
H
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
D001427:Bacterial Toxins; D047630:Depsipeptides; D008387:Marine Toxins; D015842:Serine Proteinase Inhibitors; C555914:largamide D; D002918:Chymotrypsin; D010196:Pancreatic Elastase