Conus toxins

It is not our intention to present a comprehensive review of the work on Conus toxins here the reader is referred to recent articles already in the literature (1-5). We have focused largely on fish-hunting Conus toxins, particularly the w-... 

Over 40 different types of polypeptide toxins have been found in marine animals (i). Many of these toxins are exquisitely selective in their actions, affecting a single process or receptor at minute concentrations. So far the sea anemone and gastropod Conus) toxins have attracted the most attention as molecular probes of ion channels. In this chapter, we discuss several approaches which are being used to investigate, at the molecular level, the interactions of the sea anemone neurotoxic polypeptides with sodium channels. 

Nicotinic acetylcholine Conus toxins Cone snails, Conus sp. Pain22... 

Conotoxins are the venoms of the marine cone snails. The >500 Conus species produce >10,000 different toxins. All are cysteine-rich peptides of 10-30 amino... 

Figure 15. Data from single channel experiments, plotted to show the relationship between kinetic and equilibrium parameters for several of the saxitoxins, tetrodotoxin, and Conus geographus toxin GIIIA. Compound numbering corresponds to that in Figure 1. The vertical axis is and the horizontal axis is dwell time, the reciprocal of k j. The dissociation constant, the ratio of k jj/k, therefore corresponds to distance along the diagonal. Data primarily from Ref. 95.

Between 6 and 10 homologous peptides have been extensively characterized for each toxin class. Although uj- and a-conotoxins have been isolated from several fish-hunting Conus species, x-conotoxins have so far been isolated only from C. geographus venom. 

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long and it contains 6 cysteine residues, three of which are contiguous near the amino terminus (C. Ramilo et al., unpublished results).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. 

McIntosh M, Cruz LJ, HunkapiUer MW, Gray WR, Ohvera BM. (1982) Isolation and structure of a peptide toxin from the marine snail Conus magus. Arch Biochem Biophys 218 329-334. 

Prialt [Fig. 6] is a synthetic copy of a toxin from the Magician s cone snail. Conus magus, a mollusk from the Indo-Pacific region. This is also one of the first pharmaceuticals that demonstrate the promise that marine life, particularly invertebrates, holds for drug developers. 

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. 

DHPs, dihydropyridines (eg, nifedipine) sFTX, synthetic funnel web spider toxin m-CTX, conotoxins extracted from several marine snails of the genus Conus -aga-IIIA and co-aga-IVA, toxins of the funnel web spider, Agelenopsis aperta SNX-482, a toxin of the African tarantula, Hysterocrates gigas. 

Evolution is tireless in the development of natural toxins. A vast number of variations are possible with even a small number of amino acids in peptides, and peptides make up only one of a broad array of toxic compounds. For example, the predatory marine snail genus Conus is estimated to include at least 500 different species. Each species kills or paralyzes its prey with a venom that contains 50-200 different peptides or proteins. Furthermore, there is little duplication of peptides among Conus species. Other animals with useful toxins include snakes, frogs, spiders, bees, wasps, and scorpions. Plant species with toxic (or therapeutic) substances are too numerous to mention here they are referred to in many chapters of this book. 

Com shell is carnivorous snail belongs to the world s largest genus of marine invertebrates (Conus) under the phylum of mollusks (Bingham et al., 2010). Com shell species are able to secrete venom, which contains com shell toxins (conotoxins) of bioactive peptides called as conopeptides (Layer and McIntosh, 2006). Different structural classes of... 

Olivera, . M., McIntosh, J. M., Lourdes, J. C., Luque, F. A., and Gray, W. R. (1984). Purification and sequence of a presynaptic peptide toxin from Conus geographus venom. Biochemistry 23, 5087-5090. 

The genus Conus comprises approximately five hundred species of predatory cone snails and is therefore, one of the largest, if not the largest, single genus of marine animals alive. Each species of snail produces a unique venom with between 50 and 200 components. These sulfur-rich peptides or conotoxins are neuropharmacologically active and modulate ion channel function [235]. Any attempt to deal with these toxins within this review would not be feasible and the reader is referred to other excellent reviews on the subject [235,236]. 

Bacteria, protozoa, and venomous animals synthesize numerous toxins that are used to kill their prey or to defend themselves. Sea anemones, jellyfish, cone snails, insects, spiders, scorpions, and snakes all make potent and highly specific neurotoxins. Plants form a host of alkaloids and other specialized products, some of which are specifically neurotoxic and able to deter predators. More than 500 species of marine cone snails of the genus Conus synthesize a vast array of polypeptide toxins (conotoxins), 487-489 some with unusual posttranslational modifications.490 491 The slow-moving snails are voracious predators that use their toxins, which they inject with a disposible harpoonlike tooth,492 to paralyze fish, molluscs, or worms.493... 

Cone snails, Conus spp., have been investigated because of their production of conotoxin peptides. From an evolutionary standpoint, the production of conotoxins is quite interesting due to their wide range of neurophysiological activities. The conotoxins are small peptides, 10-30 amino acids, with conformations constrained by multiple disulfide bonds that target a number of receptors in vertebrate and invertebrate nervous systems. Cone snails use these toxins to immobilize prey, which allows the relatively slow-moving cone snails to feed on fish and worms. The wide variety of conotoxins isolated and the hypervariability within peptide sequences has led some to hypothesize a combinatorial biosynthetic approach for the production of conotoxins.116117... 

Piscidin 1 and its analogues Piscidin 1 and its analogues PIIIA toxin Tetrodotoxin-resistant Na+ channel binding by p-conotoxin smlllA C. purpurascens Conus stercusmuscarum... 

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