Conotoxins and Other Conopeptides

Abstract

Conopeptides are a large family of peptide toxins produced by marine cone snails. They act with high potency and exquisite specificity on a range of ion channels and transporters of the nervous system, making them valuable drug leads and important molecular probes in neurophysiological studies. Most conopeptides are small, ranging from 10 to 30 amino acid residues, but some contain up to about 90 amino acids. They display a large chemical diversity because they have very diverse sequences and a large number of post-translational modifications. Disulfide-rich conopeptides are commonly referred to as conotoxins, and have particularly diverse structures and a broad range of molecular targets. One conotoxin, MVIIA (also named Prialt 1 or ziconotide), is an N-type calcium channel blocker that is used clinically as an analgesic to treat neuropathic pain. Other conopeptides have also attracted considerable interest for their potential pharmaceutical applications. In this chapter, the marine cone snails and their venoms are introduced and the chemical diversity of conopeptides is described, along with the techniques used to unravel this diversity. The three-dimensional structures of conopeptides are discussed and linked to their pharmacological activities.

Neuronal Nicotinic Acetylcholine Receptor Modulators from Cone Snails

“…Conopeptides have evolved to target a range of receptors, ion channels, and transporters in the central and peripheral nervous system [ 2 , 4 , 7 ]. In addition to this diversity in bioactivity, the venom compositions from the different cone snail species are also highly variable [ 2 , 8 , 9 , 10 ]. Initially, the estimated number of potential neuropharmacologically active compounds was around ~50,000 from 500 cone snail species [ 4 , 11 ].…”

Marine Natural Products from New Caledonia—A Review

“…Venomous marine cone snails (Conoidea) are neogastropod mollusks that predate on marine worms and small benthic invertebrates (thick-shelled snails, e.g., Conus textile ) or that actively “hunt” fish (thin-shelled snails, e.g., Conus geographus ) primarily by inflicting cocktails of peptide neurotoxins produced by venom glands via their modified harpoon-like radula (see review in Kaas and Craik, 2014 [ 171 ]). Fish-hunting cone snails may switch from prey-stimulated to defensive envenomation strategies as shown by the use of different and more potent “high threat” neurotoxins if threatened, the latter being regarded as a specialization in response to predation pressure from fish and cephalopods [ 172 ].…”

Bioactive Compounds Isolated from Neglected Predatory Marine Gastropods

“…Predatory marine gastropods are at a distinct disadvantage when attempting to catch larger, faster, or more agile prey; but they have evolved potent venoms to subdue their prey to compensate for their small size and slow pace [ 1 , 2 ]. The most studied marine gastropod venoms are those of the Conidae, also called Conus species and commonly named cone snails, which use a harpoon-like radula tooth to deliver potent neurotoxins.…”

“…Different Conus species feed on different prey, ranging from small fish to worms and even other gastropods [ 3 , 4 , 5 ]. The venom of each of the >700 cone snail species comprises a complex mixture of hundreds to thousands of peptides, called conopeptides; most of them target specific ion channels and transporter subtypes of the nervous system [ 1 , 2 , 6 ]. Cone snail venoms display large variability between species and even between individuals of the same species, and the total pool of cone snail peptides is estimated to be in the hundreds of thousands [ 7 , 8 , 9 ].…”