Conus Venom Peptide Pharmacology

δ-Conotoxin SuVIA suggests an evolutionary link between ancestral predator defence and the origin of fish-hunting behaviour in carnivorous cone snails

“…Cone snails are marine predators that have evolved an envenomation strategy facilitating predation on worms (vermivorous), molluscs (molluscivorous) or fishes (piscivorous) using a cocktail of venom peptides that target a range of receptors and ion channels crucial for normal physiological function [1]. Recent estimates suggest that each species of cone snail produces hundreds to thousands of conotoxins, the majority of which remain pharmacologically uncharacterized [4,17].…”

“…Recent estimates suggest that each species of cone snail produces hundreds to thousands of conotoxins, the majority of which remain pharmacologically uncharacterized [4,17]. Not surprisingly, many conotoxins affect action potential initiation and propagation, including the m-and mO-conotoxins that block the pore or alter Na V channel gating, [1,[18][19][20], the d-conotoxins that delay Na V inactivation by binding to site 6, and the i-conotoxins that enhance Na V channel opening [21][22][23]. While inhibition or enhanced activation of Na V can cause paralysis, cardiac arrhythmias or epilepsy in the case of central Na V , the precise role of conopeptides targeting Na V channels in prey capture and/or defence is unclear.…”

“…Cone snails are highly specialized marine predators that use potent venom to subdue polychaete worms, molluscs and fishes [1]. The extremely fast prey immobilization achieved by some piscivorous species represents one of the most efficient and remarkable prey-capture strategies existing in nature [2].…”

δ-Conotoxins Synthesized Using an Acid-cleavable Solubility Tag Approach Reveal Key Structural Determinants for NaV Subtype Selectivity

“…[1][2][3][4]. The majority of conotoxins are cysteine-rich and adopt rigid folded structures stabilized by multiple disulfide bridges (1)(2)(3)(4).…”

“…[1][2][3][4]. The majority of conotoxins are cysteine-rich and adopt rigid folded structures stabilized by multiple disulfide bridges (1)(2)(3)(4). Their relatively small size, high stability, and typically high affinity and selectivity for their targets make conotoxins not only useful tools to study the pharmacology of their molecular targets, but also a rich potential source of medicines, with one molecule already licensed for clinical use in pain management and several others in clinical development (5).…”