Fragment screening is one of the newest and most exciting techniques out there. Why, exactly – you ask? Well, it offers scientists who design new medicines something really special: a glimpse into the future.
With fragment screening, scientists can get away with testing only a few hundred tiny chemicals, what they call ‘fragment compounds’, to see if any of them might be the foundation for what could eventually become a new drug.
In the past, nobody thought there was useful information to be had from fragments that small – that only much bigger compounds, which are expensive and tricky to work with, could demonstrate potential to become a drug.
But we now have the technology to discern vital insights from tiny compounds – just a dozen or so atoms big. This means we know, right at the very start, whether they are worth pursuing or not.
Fragment research is a recent and burgeoning field: one with the power to help produce drugs quicker, cheaper and smarter than ever before. And it’s a big deal, because if we can anticipate the potetial of our compound right at the beginning, then time is on our side.
What is it?
Screening compounds for future drug potential is nothing new.
Drugs generally work because the chemical make-up of the medicine reacts in a precise way with proteins in the body. Proteins are the machines of life, and drugs act by binding to very specific proteins – the “targets” – in ways that suppress biological processes which support disease – like those that lead to headaches or hayfever.
And so, for years, scientists have been developing increasingly sophisticated techniques that allow them to study the interaction between their protein target and different chemical combinations in search of the perfect drug.
But it’s not always simple: in the past, we could only detect a potential drug by looking at big, complicated compounds – we just couldn’t properly study the smaller ones.
Bigger compounds mean more complexity, and more complexity means less chance of getting a successful interaction between the compound and the target. So we had to sift through many big compounds to find the future drug – a very expensive process. What’s more, regular screening can offer up a lot of red herrings: compounds that look promising but, after much time and expense, turn out not to work after all.
But fragment screening offers something different. The technique allows scientists to identify whether tiny fragments of compounds are actually connecting with the target protein. The simplicity of the fragments makes it more likely we’ll get a hit: a weak hit, but a hit nonetheless.
And because we can screen many more of these fragments, compared to the bigger, trickier compounds, we stand more chance of getting a hit – like having lots of tickets for a lottery.
But any success is then followed by the hard work of improving the potency of the compound by making small tweaks to its chemical composition, which eventually results in a lead that could generate a functional drug. Fragment screening means that we need to test far fewer compounds to find that potential drug. Scientists can identify suitable candidates early on without the hassle and heartbreak of many failed attempts.