INHIBITION OF ACETYLCHOLINESTERASE BY AN ALKYLPYRIDINIUM POLYMER FROMTHE MARINE SPONGE, RENIERA-SARAI

Large polymeric 3-alkylpyridinium salts have been isolated from the ma rine sponge Reniera sarai, They are composed of N-butyl(3-butylpyridin ium) repeating subunits, polymerized head-to-tail, and exist as a mixt ure of two main polymers with molecular weights without counterion of about 5520 and 18900. The monomer analogue of the inhibitor, N-butyl-3 -butylpyridinium iodide has been synthesized. This molecule shows mixe d reversible inhibition of acetylcholinesterase. The polymers also act as acetylcholinesterase inhibitors and show an unusual inhibition pat tern. We tentatively describe it as quick initial reversible binding, followed by slow binding or irreversible inhibition of the enzyme. Thi s kinetics suggests that there are several affinity binding sites on t he acetylcholinesterase molecule where the polymer can bind. The first binding favors binding to other sites which leads to an apparently ir reversibly linked enzyme-inhibitor complex. (C) 1998 Elsevier Science B.V. All rights reserved.