Researchers at Tel Aviv University (Israel), using an approach called rational design, are trying to develop a novel painkiller based on natural compounds found in the venom of the Israeli (family Buthidae) yellow scorpion--one of the most potent scorpions in the world--by mimicking the venom's bioactive components. The scorpion venom contains more than 300 peptides, of which only a minor fraction has been explored. Among these are the alpha-neurotoxins, which target voltage-gated sodium channels (NA(V)S) and constitute an important component in the venom of the scorpions.
The NA(V)S toxins are short polypeptides highly conserved in sequence, and three-dimensional (3D) in structure, but they differ greatly in activity and preference for insects and various mammals. Despite extensive studies of the structure-function relationship of these toxins, little is known about their evolution and phylogeny. The researchers used a broad dataset based on published sequences and rigorous cloning to reconstruct a reliable phylogenetic tree of the scorpion alpha-toxins, and estimated the evolutionary forces involved in the diversification of their genes. They thus succeeded in isolating the genetic sequences for important neurotoxins in the scorpion venom, and also developed methods to produce and manipulate the toxins. The study describing the investigation process was published on December 17, 2009, in the early online edition of Molecular Biology and Evolution.
"The mammalian body has nine different sodium channels of which only a certain subtype delivers pain to our brain,” said lead author Professor Michael Gurevitz, Ph.D., of the department of plant sciences. "We are trying to understand how toxins in the venom interact with sodium channels at the molecular level and particularly how some of the toxins differentiate among channel subtypes.”
"This new class of drugs could be useful against serious burns and cuts, as well as in the military and in the aftermath of earthquakes and natural disasters,” added Professor Gurevitz. "Instead of running the risk of addiction, this venom-derived drug, mimicking the small peptide toxin, would do what it needs to do and then pass from the body with no traces or side-effects.”
The Israeli Buthidae yellow scorpion--Leiurus quinquestriatus--also known as the Omdurman scorpion or "deathstalker”--is regarded as a highly dangerous species because its venom is a powerful cocktail of neurotoxins. One component of the venom, the peptide chlorotoxin, has shown potential for treating human brain tumors. There has also been some evidence to show that other components of the venom may aid in the regulation of insulin, and could be used to treat diabetes.
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