Performing dogs
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| Performing dogs take nerve-settling beta-blockers. Habj |
It was a question James Black asked himself in 1964 (or perhaps a bit before then), when he developed a new approach to molecular synthesis, and thus discovered propranolol hydrochloride – the compound that won him the 1988 Nobel Prize for Medicine.
An unexciting-looking chemical, it’s just two fused benzene rings and a side arm, but it’s been used to alter mood, easing aggression, phobias, and improving the social skills of people on the autism spectrum. It is used to treat PTSD, and commonly to ease performance anxiety amongst musicians and performing dogs.
Until the James Black episode, chemists approach drug synthesis like molecular roulette. They just made things. They heated stuff and mixed stuff and just generally hoped they would make something new. Then they would test it to see what it did and whether they could think of a use for it to pay for all their costly experiments. They worked secretly and didn’t collaborate, so many were repeating the work of others. In fact, it didn’t seem like chemistry had come very far since the days of alchemy at all!
James Black’s novel approach was targeted synthesis. Instead of playing lab messabouts, he studied the body and the molecules that worked in it, and tried to make similar looking ones in the lab. Propranolol hydrochloride, indeed, was designed to look a bit like adrenalin, allowing it to competitively bind to the adrenalin receptor, blocking it.
The transition to targeted design made chemistry much more successful and profitable. Since, scientists have even improved on propranolol hydrochloride, which is non-selective, making selective beta-blockers that only bind to particular receptors, along with other, unrelated targeted drugs.
But is it enough?
There is still a lot of trial and error involved, and it’s expensive to make things. Nowadays, chemists are exploring new ways of designing syntheses based on computer simulations. A great example is protein folding. By simulating how these processes work, they can come up with good targets, narrowing down the range of possible products, and increasing their chances of making something that works. But they still don’t know. It remains guesswork, and computers are only so good. Many, indeed, require vast amounts of processing power to simulate the behaviour of molecules in the body, and the number of ways proteins can fold is in fact so vast that the computers grind to a halt trying to work through all the possibilities. This just goes to show how many possibilities are out there for organic chemistry – astounding given it is the science of how only a very small number of elements can bond together!
Scientists are looking for other ways to narrow down the possibilities before computer modelling. Solvent interactions, intermolecular forces and surface interactions also play their part, and we are still working on how to model these.
James Black’s novel approach was targeted synthesis. Instead of playing lab messabouts, he studied the body and the molecules that worked in it, and tried to make similar looking ones in the lab. Propranolol hydrochloride, indeed, was designed to look a bit like adrenalin, allowing it to competitively bind to the adrenalin receptor, blocking it.
The transition to targeted design made chemistry much more successful and profitable. Since, scientists have even improved on propranolol hydrochloride, which is non-selective, making selective beta-blockers that only bind to particular receptors, along with other, unrelated targeted drugs.
But is it enough?
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| Before James Black, chemists played molecular roulette. Ralf Roletschek via Wikipedia Commons. |
There is still a lot of trial and error involved, and it’s expensive to make things. Nowadays, chemists are exploring new ways of designing syntheses based on computer simulations. A great example is protein folding. By simulating how these processes work, they can come up with good targets, narrowing down the range of possible products, and increasing their chances of making something that works. But they still don’t know. It remains guesswork, and computers are only so good. Many, indeed, require vast amounts of processing power to simulate the behaviour of molecules in the body, and the number of ways proteins can fold is in fact so vast that the computers grind to a halt trying to work through all the possibilities. This just goes to show how many possibilities are out there for organic chemistry – astounding given it is the science of how only a very small number of elements can bond together!
Scientists are looking for other ways to narrow down the possibilities before computer modelling. Solvent interactions, intermolecular forces and surface interactions also play their part, and we are still working on how to model these.
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