Tetrodotoxin, the poison found in pufferfish, is an essential tool for neuroscience research, and a better technique to synthesise it could boost research into drugs that relieve pain
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A quicker way of making one of the world’s most potent neurotoxins could lead to novel drugs for pain relief and to a better understanding of how the body’s pain system works.and sea snails, but is actually made by bacteria. It has a remarkable ability to block sodium ion channels, which nerves use to send signals, and just a few milligrams of it are enough to cause bodily paralysis and death in humans.
Although TTX is arguably one of the most potent blockers of sodium ion channels, the difficulty in synthesising it has meant that progress in developing drugs by using it has been slow, saysNow, Trauner and his colleagues have designed a 22-step process that results in 11 per cent of the ingredients used being turned into tetrodotoxin. This is a 10-fold improvement on previous techniques to create it and reduces the number of steps by at least a third.
The synthesis relies on producing a key part of the molecule in a different way. Rather than adding nitrogen-based fragments to the core carbon structure of tetrodotoxin, Trauner and his colleagues add a carbon fragment. Swapping out a carbon-nitrogen bond for a carbon-carbon bond allows them to simplify the entire process, says Trauner.
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