conotoxins

Conotoxins are a diverse class of peptide toxins produced by marine cone snails (genus Conus) as part of their venom. Each snail's venom contains numerous distinct conotoxins, enabling rapid immobilization of prey and defense against predators.

Chemistry and structure: Most conotoxins are short peptides, typically 10–40 amino acids long, stabilized by multiple disulfide bonds. They often feature the cystine knot motif and undergo extensive post-translational modifications, contributing to stability, potency, and receptor selectivity.

Targets and mechanisms: Conotoxins act on components of the nervous system, especially ion channels and receptors. They include blockers and modulators of voltage-gated calcium, sodium, and potassium channels, as well as ligand-gated receptors such as nicotinic acetylcholine receptors and other neurotransmitter targets. They are commonly grouped into pharmacological families such as alpha-conotoxins (nicotinic receptors), omega-conotoxins (N-type calcium channels), mu-conotoxins (sodium channels), and delta- or kappa-conotoxins (modulating channel gating or potassium channels).

Applications and significance: The most notable conotoxin-derived drug is ziconotide (MVIIA), an omega-conotoxin approved for severe chronic pain and administered intrathecally. Beyond therapeutics, conotoxins serve as powerful research tools for studying ion channels and receptors and for exploring structure–activity relationships in neural targets. Many conotoxins are in preclinical development, reflecting their potential as highly selective pharmacological probes and leads for drug discovery.

Diversity and evolution: Cone snails produce hundreds of distinct conotoxins, and the broad species diversity yields a rich repertoire with wide pharmacological reach. Synthetic and recombinant approaches are used to study and harness their properties, with careful handling due to their potent biological activity.