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 fir st members of this family have been characterized from the eastern Pac ific species, Conus purpurascens (the purple cone); three peptides tha t cause paralysis in fish were purified and characterized from milked venom, The sequence and disulfide bonding pattern of one of these, alp ha A-conotoxin PIVA, is as follows: [GRAPHICS] where O represents tran s 4-hydroxyproline. The two other peptides purified from C. purpurasce ns venom are the under-hydroxylated derivatives, [Pro(13)]alpha A-cono toxin PIVA and [Pro(7,13)]alpha A-conotoxin PNA. The peptides have bee n chemically synthesized in a biologically active form, Both electroph ysiological experiments and competition binding with alpha-bungarotoxi n demonstrate that alpha A-PIVA acts as an antagonist of the nicotinic acetylcholine receptor at the postsynaptic membrane.