Conus venom

These include nicotinic acetylcholine receptors, neuronal calcium channels, muscle sodium channels, vasopressin receptors, and iV-methyl-D-aspartate (NMDA) receptors. Some general features of the structure, function, and evolution of biologically active peptides isolated from Conus venom are presented. 

Like the other paralytic toxins from Conus venom, a-conotoxins are small and very tightly folded, structural features which may be advantageous for rapid paralysis of prey (1). a-Conotoxins are typically 13 to 15 amino acids long with two disulfide bridges (see Table III). In addition to the five a-conotoxins shown, two new a-conotoxins (SIA and SIB) from C. striatus have recently been isolated, sequenced, and chemically synthesized. SIA is very unusual because it is 19 amino acid residues long and it contains 6 cysteine residues, three of which are contiguous near the amino terminus (C. Ramilo et al., unpublished results). 

The a -, /z-, and a-conotoxins are the best characterized of the peptides isolated from Conus venoms so far. However, a large number of other peptides are found in these venoms. These comprise both paralytic toxins to immobilize the prey of the cone snail, and other biologically active peptides which are not themselves directly paralytic. Only the briefest overview of these peptide components will be presented here. 

A large number of other non-paralytic but biologically active peptides have been purified and sequenced. In most cases however, the detailed mechanism of action has not yet been elucidated. Clearly, Conus venoms will be a rich source of such peptides that can be used to probe various receptor targets, particularly in the central nervous system. 

Terlau, H. and Olivera, B. M. Conus venoms a rich source of novel ion channel-targeted peptides. Physiol. Rev. 84 41-68, 2004. 

It was observed that for CCK and related peptides sulfation of the tyrosine residue is essential for triggering the full hormonal response.131 32 More recently, additional sulfated peptides have been identified as CCK-58, 135 phytosulfokinine-a, as peptide growth factor in plants 136 as well as various toxins from Conus venom. 137138 This observation has fostered intensive research to develop synthetic methods for efficient production of tyrosine O-sulfated peptides by chemical and enzymatic approaches. 

Olivera, B. M., Conus venom peptides, receptor and ion channel targets, and drug design 50 million years of neuropharmacology, Mol. Biol. Cell, 8, 2101, 1997. 

MS Based Scanning Methodologies Applied to Conus Venom... 

The next class of endogenous peptides discovered in Conus venom was the contulakins, which are peptide homologues to neurotensin. The contulakins are currently the only member of the neurotensin family to have been isolated from an invertebrate and bind to three known neurotensin receptor subtypes with a significantly higher potency than neurotensin itself and therefore have therapeutic potential for pain prevention. 

B.M. Post-translationally modified neuropeptides from Conus venoms. Eur. J. Biochem. 1999, 264, 271-275... 

Table 23.9 Bibliographic data on amino acid sequences of some Conus venoms...

Initial interest on Conus venoms focused on the most dangerous species Conus geographus), as well as other species that have inflicted serious envenomations in humans. C. geographus, the species responsible for most human deaths, has an estimated fatality rate of 70% compared to the overall rate of <40% for all species (Yoshiba, 1984). Death is attributed mainly to paralysis of the diaphragm muscle with consequent respiratory failure (Cruz and White, 1995). Compared to neurotoxic snakebites, the onset of symptoms in Conus... 

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