Toxins polypeptides

The polypeptide toxins from the scorpions Centruroides suffusus and Tityus ser-rulatus. These toxins act by shifting the voltage dependence of the activation of Na channels, thereby inducing a Na channel activity at negative potentials at which Na channels are normally closed 63,64). Site 4 toxins, because of their high affinity for the Na channel, have been efficient tools to elucidate the molecular structure of the Na channel 30,65,66). 

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. 

KEM ET AL. Sea Anemone Polypeptide Toxins Affecting Sodium Channels... 

Thiolation of Gelonin (or Other Single-Polypeptide Toxins) with 2-Iminothiolane (Traut s Reagent)... 

Synthetic drugs of comparable selectivity and affinity to the 1,4-dihydropyridines do not yet exist for the other channel types, T, N, P/Q, and R these remain characterized by complex polypeptide toxins of the aga- and conotoxin classes. Neuronal pharmacology, including that of the central nervous system (CNS), is dominated by the N, P/Q, and R channels. This underscores the normally weak effect of L-channel antagonists on CNS function. Drugs that act at the N, P, and R channels with comparable selectivity and affinity to the 1,4-dihydropyridines may be expected to offer major potential for a variety of CNS disorders, including neuronal damage and death from ischemic insults. 

Each type of channel is a unique protein which, in principle, could be uniquely targeted for purposes of drug design. Q- and R-type channels have also been described on the basis of polypeptide toxin binding studies, but have not been extensively exploited for... 

Certain species of sea anemones produce basic polypeptide toxins of molecular weights ranging from 2500 to 5000 daltons. They cause persistant activation of sodium channels and lead to paralysis. This is very helpful to the sea anemone is harvesting its prey. 

Predatory cone snails produce a variety of polypeptide toxins... 

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... 

England LJ, Imperial J, Jacobsen R, Craig AG, Gulyas J, Akhtar M, Rivier J, Julius D, Olivera BM (1998) Inactivation of a Serotonin-Gated Ion Channel by a Polypeptide Toxin from Marine Snails. Science 281 575... 

Scorpionid secretions represent a mixture of neurotoxic polypeptide toxins, proteolytic and hemolytic enzymes (phospholipases A, acetylcholinesterases, ribonucleases, hyaluronidases), and biogenic amines (serotonin, tryptamine, histamine). The polypeptide toxins (the so-called scorpamines) contain fewer than 40 or 60-76 mostly alkaline and aromatic amino acids stabilized by four disulfide bridges.20 96... 

Olsnes S, Sandvig K (1985) Entry of polypeptide toxins into animal cells. In Endocytosis (Pastan I, Willingham MC, eds), pp 195-234, Plenum pubi corp, NY. 

Calcium-channel blockers - polypeptide toxins A number of peptide marine snail, snake, beede and spider toxins block one or other of the many subsets of Ca -channels see CALCIUM-CHANNEL BLOCKERS. These include the fi>-agatoxtns... 

Chloride-channel blockers - polypeptide toxins. The scorpion toxin chlorotoxin blocks small-conductance Cl -channels from rat enterocytes. See CHLORIDE-CHANNEL BLOCKERS. 

Basic polypeptide toxin from rattlesnake Crotalus terrificus. Activates sodium channels in muscle depolarization and contracture, blocked by tetrodotoxin. See also crotoxin. 

Amino acid polypeptide toxin from Eastern green mamba (Dendroaspis augusticeps). Inhibits potassium channels and facilitates release of ACh at nerve terminals increases evoked release but does not produce spontaneous release of ACh. 

Polypeptide toxins of about 33 amino acid derived from the Red Sea flat fish Pardachirus mar-moratus and other P. species. LD50, mice 25 mg/kg IP. Pardaxins are ionophores that have neurotoxic and haemolytic effects. The toxins also act as shark repellents. 

Schwann cells of squid axons (J. Villegas et al. 1976), ghoma cells (Reiser and Hamprecht 1983), and other preparations. In most of these preparations certain polypeptide toxins (e.g., from sea anemones or scorpions) act synergistically, as in spiking cells, but in contrast are often less sensitive to tetrodotoxin (equilibrium constant of inhibition fTi=l iM in C9 cells Romey et al. 1979). 

---