Scientists have synthesized pufferfish venom tetrodotoxin in 22 steps

An international team of researchers from Germany, the USA, and Japan developed a short synthesis method tetrodotoxin(TTX). This is a deadly natural poison that the body of puffer fish produces. The team proposed a 22-step process. It allows the creation of a biologically active analog of a neurotoxin from available materials. The method is 30 times more effective than all existing ones. It is very helpful to develop a new generation of painkillers.

Tetrodotoxin, in addition to pufferfish, is produced by some poisonous snails, octopuses, newts, frogs, and worms. For scientists, it still remains an unexplored mystery: the compound has a complex structure and is extremely unstable when isolated from living beings. Creating a chemical copy of it in the laboratory so that the toxin can be produced on a large scale has been unsuccessfully tried in different parts of the world since the end of the 19th century.

A new research team has unveiled a synthesis of a highly effective tetrodotoxin that starts with a glucose derivative. It involves 22 steps, which the developers say is the shortest route. As a result, scientists get 11% of the substance from the original commercially available materials, which is considered an impressive result.

What is all the work for?

Animals use this compound in self-defense: tetrodotoxin is a powerful paralytic. It easily and quickly absorbs into the bloodstream and clogs the sodium conducting channels in the membranes of nerve cells, acting as a plug. Thus, the toxin blocks the conduction of impulses in the nerve circuits.

TTX is very dangerous to humans because it stops nerves from sending signals to muscles, which can lead to paralysis. However, it may have other uses in other organisms, such as acting as a pheromone or a feeding stimulant. But the fact that TTX blocks nerves are interesting to researchers because it could lead to a new class of painkillers that don’t have the same addictive qualities as opioids.

It expects to use these abilities to create a new generation of effective painkillers:

Scientists expect to use these abilities to create a new generation of effective painkillers. There is the involvement of nerve signals. We also see additional suppression of tetrodotoxin in the body’s sensation of pain. That is why scientists are trying very hard to learn how to produce it.

There has long been a great need in medicine for new mechanisms of anesthesia that would not cause addiction and side effects such as opioids. The authors of the method plan to use it as a platform for further development of neurotoxin derivatives.

“There is a huge medical need for painkillers that work in new ways, especially ones that don’t work like opioids. It is interesting that tetrodotoxin can block nerve signals. These nerve signals are a big part of how we feel pain. Because of this, tetrodotoxin will help to make non-addictive painkillers for the future “said Trauner.

“The most difficult parts of making tetrodotoxin are its high level of chemical complexity, its chemical instability, and how hard it is to purify and isolate. The fact says that the previous synthesis took more steps and was less effective overall “Trauner continued.

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