Author:

Keywords:

alpha-conotoxin, Cone snail, electrophysiology

Abstract:

Cone snails (genus Conus) are marine species that evolved as specialized predators by developing the most sophisticated peptide chemistry and neuropharmacology in their venom. These venom peptides, called neurotoxins or conotoxins are generally small cysteine-rich peptides with the unique feature to be highly selective and potent ligands for a wide range of ion channels and receptors. Consequently, they are recognized as lead compounds in the quest for new therapeutics in diseases such as Parkinson’s disease, Alzheimer’s disease, pain and many other neurological disorders. Here, we present the purification and characterization of several novel conotoxins from three cone snail species: C. asiaticus, C. australis and C. longurionis. From the venom of C. asiaticus, we isolated a conotoxin with framework III (CC-C-C-CC) and a molecular mass of 1702.04 Da. Another peptide from this species can be classified in framework XIV (C-C-C-C) with a molecular mass of 1699.93 Da. Concerning the venom of C. australis, we purified an α-conotoxin belonging to a new subclass of this family. The molecular mass of the peptide, having the typical CC-C-C framework, is 1762.06 Da. From the third cone snail species, C. longurionis, we purified two peptides, classified in the O-superfamily of conotoxins, having a molecular mass of 2589.00 Da and 2781.13 Da respectively. The revelation of their pharmacological targets includes screening on neuronal and muscle subtype nicotinic acetylcholine receptors as well as voltage-gated ion channels (NaV, KV) using heterologous expression in an electrophysiological bio-assay.