2.0 Experimental Approach
Predatory cone snails (genus Conus) produce a rich array of venoms that collectively contain an estimated 100,000 small, disulfide-rich peptides (i.e., conotoxins, or conopeptides). Over the last few decades, the conopeptides have revealed a remarkable diversity of pharmacological function and utility. An evolutionary rationale for the existence of such a large and pharmacologically diverse set of gene products can be premised on the complexity of intra- and interspecies interactions that define the ecology of Conus snails. Insights into these evolutionary trends, moreover, have been exploited with great neuropharmacological success, so that research into the Conus snails effectively recapitulates a new concerted discovery approach, which we discuss here, for developing unique ligands for both laboratory and therapeutic applications. Methods. Three adult specimens of C. geographus, which were collected from the Gould reef, and then were put into tank. Their toxin was collected by milking procedure, they applied light pressure on their shell, and thus they will sting their proboscis and eject their venom. After venom was collected they stored it in 20º C. Researches trying to answer question on the defense-evoked venom behavior in Conus geographus, and the location of their toxins. Conus venoms contain a remarkable diversity of pharmacologically active small peptides. …show more content…
Their targets are ion channels and receptors in the neuromuscular system. The venom of Conus geographus contains high-affinity peptides that act on voltage-sensitive calcium channels, sodium Channels, N-methyl-D-aspartate (NMDA) receptors, acetylcholine receptors, and vasopressin receptors; many more peptides with still uncharacterized receptor targets are present in this venom. It now seems that the Conus species (approximately 500 in number) will each use a distinctive assortment of peptides and that the pharmacological diversity in Conus venoms may be ultimately comparable to that of plant alkaloids or secondary metabolites of microorganisms. The cone snails may generate this diverse spectrum of venom peptides by a "fold-lockcut" synthetic pathway. The major pharmacologically active molecules in all Conus venoms are small peptides, 10 to 30 amino acids in length. Most are exceptionally rich in disulfide bonds. Almost invariably, Conus toxins are smaller than polypeptide toxins used by other venomous animals. Spider, scorpion, and snake venoms all contain toxins that are typically between 40 and 100 amino acids in length in certain cases, for instance, β-bungarotoxin, they may be even larger. Thus, although in elapid snakes (such as cobras), paralytic toxins that target to the acetylcholine receptor are polypeptides of 60 to 80 amino acids, in fish-hunting cone snails the analogous …show more content…
When all available ա-conotoxins sequences are compared, only the cysteine residues involved in disulfide bonding, and one glycine residue are invariant.
Indeed, no ա-conotoxin sequence (nor any other peptide of known sequence in Conus venoms) has been found in more than one venom. Each cone venom appears to have its own distinctive signature of conotoxin sequences.
These peptides are now standard research tools in neuroscience. The µ-conotoxins, because of their ability to preferentially block muscle but not axonal Na+ channels, are convenient tools for immobilizing skeletal muscle without affecting axonal or synaptic events. The ա-conotoxins have become standard pharmacological reagents for investigating voltage-sensitive Ca2+ channels and are used to block presynaptic termini and neurotransmitter release.
Conotoxins are also used in medical diagnosis; an immunoprecipitation assay with radiolabeled ա-conotoxin can be used to diagnose the Lambert-Eaton myasthenic syndrome (16), a disease
Predatory cone snails (genus Conus) produce a rich array of venoms that collectively contain an estimated 100,000 small, disulfide-rich peptides (i.e., conotoxins, or conopeptides). Over the last few decades, the conopeptides have revealed a remarkable diversity of pharmacological function and utility. An evolutionary rationale for the existence of such a large and pharmacologically diverse set of gene products can be premised on the complexity of intra- and interspecies interactions that define the ecology of Conus snails. Insights into these evolutionary trends, moreover, have been exploited with great neuropharmacological success, so that research into the Conus snails effectively recapitulates a new concerted discovery approach, which we discuss here, for developing unique ligands for both laboratory and therapeutic applications. Methods. Three adult specimens of C. geographus, which were collected from the Gould reef, and then were put into tank. Their toxin was collected by milking procedure, they applied light pressure on their shell, and thus they will sting their proboscis and eject their venom. After venom was collected they stored it in 20º C. Researches trying to answer question on the defense-evoked venom behavior in Conus geographus, and the location of their toxins. Conus venoms contain a remarkable diversity of pharmacologically active small peptides. …show more content…
Their targets are ion channels and receptors in the neuromuscular system. The venom of Conus geographus contains high-affinity peptides that act on voltage-sensitive calcium channels, sodium Channels, N-methyl-D-aspartate (NMDA) receptors, acetylcholine receptors, and vasopressin receptors; many more peptides with still uncharacterized receptor targets are present in this venom. It now seems that the Conus species (approximately 500 in number) will each use a distinctive assortment of peptides and that the pharmacological diversity in Conus venoms may be ultimately comparable to that of plant alkaloids or secondary metabolites of microorganisms. The cone snails may generate this diverse spectrum of venom peptides by a "fold-lockcut" synthetic pathway. The major pharmacologically active molecules in all Conus venoms are small peptides, 10 to 30 amino acids in length. Most are exceptionally rich in disulfide bonds. Almost invariably, Conus toxins are smaller than polypeptide toxins used by other venomous animals. Spider, scorpion, and snake venoms all contain toxins that are typically between 40 and 100 amino acids in length in certain cases, for instance, β-bungarotoxin, they may be even larger. Thus, although in elapid snakes (such as cobras), paralytic toxins that target to the acetylcholine receptor are polypeptides of 60 to 80 amino acids, in fish-hunting cone snails the analogous …show more content…
When all available ա-conotoxins sequences are compared, only the cysteine residues involved in disulfide bonding, and one glycine residue are invariant.
Indeed, no ա-conotoxin sequence (nor any other peptide of known sequence in Conus venoms) has been found in more than one venom. Each cone venom appears to have its own distinctive signature of conotoxin sequences.
These peptides are now standard research tools in neuroscience. The µ-conotoxins, because of their ability to preferentially block muscle but not axonal Na+ channels, are convenient tools for immobilizing skeletal muscle without affecting axonal or synaptic events. The ա-conotoxins have become standard pharmacological reagents for investigating voltage-sensitive Ca2+ channels and are used to block presynaptic termini and neurotransmitter release.
Conotoxins are also used in medical diagnosis; an immunoprecipitation assay with radiolabeled ա-conotoxin can be used to diagnose the Lambert-Eaton myasthenic syndrome (16), a disease