CHARACTERIZATION OF ALPHA-CONOTOXIN INTERACTIONS WITH THE NICOTINIC ACETYLCHOLINE-RECEPTOR AND MONOCLONAL-ANTIBODIES

The venoms of predatory marine cone snails, Conus species, contain num erous peptides and proteins with remarkably diverse pharmacological pr operties. One group of peptides are the alpha-conotoxins, which consis t of 13-19 amino acids constrained by two disulphide bonds. A biologic ally active fluorescein derivative of Conus geographus alpha-conotoxin GI (FGI) was used in novel solution-phase-binding assays with purifie d Torpedo californica nicotinic acetylcholine receptor (nAchR) and mon oclonal antibodies developed against the toxin. The binding of FGI to nAchR or antibody had apparent dissociation constants of 10-100 nM. St ructure-function studies with alpha-conotoxin GI analogues composed of a single disulphide loop revealed that different conformational restr aints are necessary for effective toxin interactions with nAchR or ant ibodies.