The venom from the marine gastropods of the Conus genus (commonly referred to as cone snails) represents a significant natural drug library for research in neuropharmacology. It is considered that of the ~700 species of the genus, each species produces 1000-1900 unique peptides in their venom and less than 0.1% of these are currently pharmacologically characterized (Davis et al. 2009). The major component that is predominately responsible for the venoms rapid paralytic effects are small, disulfide rich peptides known as conotoxins. Conotoxins display exquisite potency and high selectivity for a range of both ligand and voltage gated ion channels and hence have been implicated as potential drug leads for a range of neurological disorders .
Cone snails use a hollow radula referred to as the harpoon delivery system for envenomation, which has been linked to both predatory and defensive behaviours. Recent research of the C.geographus (known to be fatal to humans)and C.marmoreus species discovered the notable ability of cone snails to rapidly switch between venoms with distinctive peptide compositions based on either defensive or predatory stimulation (Duterte et al. 2014). Each venom type displayed distinguishing pharmacological profiles; with initial analysis showing the defensive venom of C.geographus targeted multiple human ion channels, whilst the predatory venom was mostly inactive at human targets (Duterte et al. 2014). These findings resulted in new proposals for cone snail evolution, as well as creating an opportunity to develop a rational drug discovery strategy. To expand on these findings and develop a greater understanding of the distinctive venoms’ function and their differences, structural genomes of each will be characterized by analysis of individual conotoxins. Here using 2D-NMR, we investigate the structure of the conotoxin Geo3330, identified as a prominent peptide of the species C.geographus’ predatory venom.