Conotoxins: peptide toxins from cone snails

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Conotoxin: peptide toxins from cone snails

Cone snails are venomous marine molluscs, thriving in tropical marine habitats. About 600-700 species have been identified so far. Their venoms contain a large number of peptide toxins, from 100 to 1000 or more depending on species. These peptides are named conotoxins.

Conotoxins are generally made of 15 to 30 amino acids and have generally between 2 and 3 disulfide bridges. Conotoxins target and block potently a wide range of ion channels, such as voltage-gated sodium channels (Nav), voltage-gated calcium channels (Cav), voltage-gated potassium channels (Kv), nicotinic acetylcholine receptors (nAchRs) as well as other membrane receptors.

Conotoxins are useful molecular tools for studying the properties of their targets in normal and diseases states and can also demonstrate therapeutic interest as peptide-based drugs. Conotoxins are classified in several families [1-5].

Conotoxin classification

α-conotoxins

α-conotoxins are nicotinic acetylcholine receptor (nAChR) antagonists located in nerves and muscles. Some α-conotoxins block nAChRs at the neuromuscular junctions such as α-conotoxin MI, while others are selective blockers of neuronal nAChRs such as α-conotoxin IMI [6].

Smartox offers a range of α-conotoxins:

µ-conotoxins

μ-conotoxins target voltage-dependent sodium channels (Nav) preferentially in excitable cells of skeletal muscle. µ-conotoxins are usually formed by 22–25 amino acids and contain six cysteine residues forming three disulfide bridges [7].

Smartox Biotechnology offers a range of µ-conotoxins:

ω-conotoxins

ω-conotoxins are potent inhibitors of N-type voltage-dependent calcium channels (VDCC) [8]. ω-conotoxin MVIIA, also named ziconotide, a N-type selective VDCC isolated from C. magus, was the first conotoxin to be approved as drug under the name of Prialt for the treatment of severe and chronic pain [9].

Smartox biotechnology offers a range of ω-conotoxins:

δ-conotoxins

δ-conotoxins bind to voltage-dependent sodium channels and inhibit them.

κ-conotoxins

κ-conotoxins target potassium channels and may result in enhanced neuronal excitability. Few κ-conotoxins such as κ-conotoxin RIIIJ, κ-conotoxin RIIIK or κ-conotoxin PVIIA have been characterized to date

Conantokins

Conantokins act as potent and specific antagonists of the N-Methyl-D-Aspartate receptor (NMDAr) and contain multiple γ-carboxyglutamate (Gla) amino acid residues.

Smartox Biotechnology offers the conantokin G, a selective antagonist of the NR2B subunit of NMDAr that exhibits neuroprotective properties.

Conopressins

These cone snail peptides are modulators of vasopressin/oxytocin receptors. Smartox Biotechnology offers Lys-conopressin G.

Get conotoxins from Smartox Biotechnology

Smartox Biotechnology is specialized in chemical synthesis and engineering of conotoxins and other peptide toxins issued from animal venoms. The company offers a wide range of animal toxins for life-sciences research, including some very innovative ones such as the fluorescently labeled Stichodactyla toxin – ShK. Feel free to browse our online catalog to discover reagents you need or request the synthesis of your own toxin.

References

[1] Adam D., et al. (1996) Conotoxins and Their Potential Pharmaceutical Applications. Drug Development Research
[2] Lewis R., et al. (2012) Conus Venom Peptide Pharmacology. Pharmacological Reviews. PMID: 22407615
[3] Olivera B., Cruz L. (2001) Conotoxins, in retrospect. Toxicon. PMID:10936619
[4] Terlau H., Olivera BM. (2004) Conus venoms: a rich source of novel ion channel-targeted peptides. Physiological Reviews. PMID:14715910
[5] Olivera BM, et al. (1985) Peptide neurotoxins from fish-hunting cone snails. Science
[6] Lebbe E., et al.(2014) Conotoxins Targeting Nicotinic Acetylcholine Receptors: An Overview. Mar drugs. PMID:24857959
[7] Li R., Tomaselli G. (2004) Using the deadly μ-conotoxins as probes of voltage-gated sodium channels. Toxicon. PMID:15246758
[8] Hannon HE., Atchison WD. (2013) Omega-conotoxins as experimental tools and therapeutics in pain management. Mar Drugs.PMID:23470283
[9] Miljanich GP. (2004) Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Current Medicinal Chemistry. PMID:15578997