Enzyme inhibitor
These furanocembrenolide-class diterpenes (FWBipinnatin-A = 488.49 g/mol; CAS (Bipinnatin A) = 99552-28-0; FWBipinnatin-B = 458.46 g/mol; CAS (Bipinnatin B) = 99552-24-6; FWBipinnatin-C = 460.48 g/mol; CAS (Bipinnatin C) = 123483-20-5), isolated from the bipinnate sea plume Antillogorgia bipinnata, a sea fan found in the eastern Caribbean Sea, are naturally occurring marine neurotoxins that irreversibly inhibit nicotinic acetylcholine receptors by forming a covalent bond with Tyrosine-190 in the a-subunit of the receptor (See also Lophotoxin). The parent species of the bipinnatins display little, if any, affinity for the nicotinic receptor. Preincubation of the toxins appeared to produce a single, relatively stable, active toxin species that irreversibly inhibited the two acetylcholine-binding sites on the nicotinic receptor with two distinguishable apparent pseudo first-order rates. The difference in the rates of irreversible inhibition of the two binding sites on the receptor was exploited to selectively inhibit one site for the pharmacological investigation of the other. The bipinnatins preferentially inhibited the binding site near the ad-subunit interface that displays low affinity for metocurine and high affinity for acetylcholine. The bimolecular reaction constants for the interaction of the bipinnatins with the nicotinic receptor decreased in the order: Bipinnatin-B > Bipinnatin-A > BipinnatinC, for both acetylcholine-binding sites. The ratio of the bimolecular reaction constants for the two binding sites on the receptor was not the same for the three bipinnatins, suggesting that the reaction of the bipinnatins with the nicotinic receptor is sensitive to differences in the structure of the two acetylcholine-binding sites.
