A NEW FAMILY OF CONUS PEPTIDES TARGETED TO THE NICOTINIC ACETYLCHOLINE-RECEPTOR

In this work, a new family of Conus peptides, the alpha A-conotoxins, which target the nicotinic acetylcholine receptor, is defined, The first members of this family have been characterized from the eastern Pacific species, Conus purpurascens (the purple cone); three peptides that cause paralysis in fish were purified and characterized from milked venom, The sequence and disulfide bonding pattern of one of these, alpha A-conotoxin PIVA, is as follows: [GRAPHICS] where O represents trans 4-hydroxyproline. The two other peptides purified from C. purpurascens venom are the under-hydroxylated derivatives, [Pro(13)]alpha A-conotoxin PIVA and [Pro(7,13)]alpha A-conotoxin PNA. The peptides have been chemically synthesized in a biologically active form, Both electrophysiological experiments and competition binding with alpha-bungarotoxin demonstrate that alpha A-PIVA acts as an antagonist of the nicotinic acetylcholine receptor at the postsynaptic membrane.