Rational drug design

[Snorlax]

I was going through the study design, and saw this.
I'v heard of it, but never needed to study it. What is it?!

[Yacoubb]

You don't need to know about it specifically; however, rational drug design refers to the development of a drug that specifically inhibits the active sites of a pathogenic agent (I.e. a competitive inhibitor) and thereby hinders the ability of the pathogen to carry out its pathogenic function and potentially cause disease.

[vox nihili]

You don't need to know about it specifically; however, rational drug design refers to the development of a drug that specifically inhibits the active sites of a pathogenic agent (I.e. a competitive inhibitor) and thereby hinders the ability of the pathogen to carry out its pathogenic function and potentially cause disease.

This is pretty close but not quite it. The idea behind rational drug design is that you study the biology of the target and then exploit a particular structure of that organism/virus.

So a couple of examples:

Antibiotic design tends to focus on bacterial ribosomes. They're something that we don't have in common with bacteria, as they're hugely different in their structure. So by targeting ribosomes or ribosome synthesis, we can damage bacteria and not ourselves. Though, it should be noted that people can often get a little sick on antibiotics because bacterial ribosomes are similar to mitochondrial ribosomes.
Another one: protists (which are eukaryotes too) are really hard to target because there are few structural/biochemical differences. This makes them extremely difficult to treat as we often end up poisoning ourselves in the process. That's part of the reason malaria is such a problem. We can easily kill it, but find it difficult to do without harming ourselves. Traditional treatments target an enzyme they use to produce acetate (enzyme is called PFO). Another possible method of treatment is to try to shut down the chloroplast in the malaria parasite (a UniMelb discovery btw woo!).

Drug design traditionally was just trial and error with bioassays and things like that. So you'd culture a whole heap of the thing you're trying to knock off and just see what kills it. Nowadays we can be a little more sophisticated.
The reason I've made a point of trying to clear it up though is that it is really, really quite interesting and shows just how important studying the biology of other organisms (and not just humans) is!

[slothpomba]

There are many ways in which drugs are discovered or created.

You have serendipity where they're discovered by pure coincidence . Many more drugs than you think were discovered this way (indeed, scientific knowledge in general), the famous example would be penicillin. He wasn't looking to make it or find it but Florey did. That's serendipity in the lab. You have it in the clinic too. There are many drugs that come to mind but Viagra (before it was sold as Viagra obviously) was originally created to treat heart problems. Some very observant nurses noticed it had...other effects.

There's the territory of modifying the chemical structure of drugs we already have to create new ones. It might not be very obvious at this level of biology/chemistry but small changes can lead to significant differences.

Finally, like T-Rav said we have also have random screening. Drug companies have huge chemical libraries (and robots) to test their library of millions of chemicals to find something that does what they want.

Rational drug design i think is best looked at in contrast to all these methods. Key emphasis is on the design bit. Rather than finding something that works without necessarily paying to much mind to the structure (grossly inaccurate but good enough for vce), in rational drug design, you design the drug to fit the disease. It's a new and different way of looking at it compared to the other ways. It's purposely designed to do x. In the case given in VCE bio, relenza was specifically designed to interfere with viruses. They wanted that property and made a new molecule with it rather than discovering one by mistake or trying a bunch of existing molecules.

Probably gave you a bit of overkill but it'll give you an insight into the pharma industry and why rational drug design is special.

Drug design traditionally was just trial and error with bioassays and things like that.

Actually...still kinda is :p

[vox nihili]

There are many ways in which drugs are discovered or created.

You have serendipity where they're discovered by pure coincidence . Many more drugs than you think were discovered this way (indeed, scientific knowledge in general), the famous example would be penicillin. He wasn't looking to make it or find it but Florey did. That's serendipity in the lab. You have it in the clinic too. There are many drugs that come to mind but Viagra (before it was sold as Viagra obviously) was originally created to treat heart problems. Some very observant nurses noticed it had...other effects.

There's the territory of modifying the chemical structure of drugs we already have to create new ones. It might not be very obvious at this level of biology/chemistry but small changes can lead to significant differences.

Finally, like T-Rav said we have also have random screening. Drug companies have huge chemical libraries (and robots) to test their library of millions of chemicals to find something that does what they want.

Rational drug design i think is best looked at in contrast to all these methods. Key emphasis is on the design bit. Rather than finding something that works without necessarily paying to much mind to the structure (grossly inaccurate but good enough for vce), in rational drug design, you design the drug to fit the disease. It's a new and different way of looking at it compared to the other ways. It's purposely designed to do x. In the case given in VCE bio, relenza was specifically designed to interfere with viruses. They wanted that property and made a new molecule with it rather than discovering one by mistake or trying a bunch of existing molecules.

Probably gave you a bit of overkill but it'll give you an insight into the pharma industry and why rational drug design is special.

Actually...still kinda is :p

hahah the viagra reference... beautiful. That's all really interesting! Love that stuff, pity I'm a total muppet with chemistry.




FYI everyone as well, the drug I was talking about doesn't target PFO, it makes use of PFO to be activated then it goes and mucks up DNA synthesis (was typing Biol notes about it as I was writing my last post, so figured it was relevant—also sure there'll be someone who've read that and thought "ahh t-rav, so, so wrong!")

[Smiley_]

so what should we know for the exam on it?

[vox nihili]

so what should we know for the exam on it?

Just that it refers to designing drugs to target specific structures, rather than just seeing what works. So you need to be able to connect the idea of studying the biology, then making the drug to target a specific structure that you've learned about.