Some machines are heralding a new era of rational drug design.
Prof Andrew Harrison is CEO of Diamond Light Source Ltd, which manages Britain’s national synchrotron facility through funding from the British Government and a research charity called the Wellcome Trust. Diamond is one of 70 such machines around the world, but it’s one of the newest and most advanced.
An inorganic chemist by training, Harrison explains via e-mail why research happening at Diamond is ground-breaking, particularly in the area of drug design. “Traditionally, drug developers worked without knowing the structure of the protein they were targeting,” explains Harrison. “So they had to screen many chemical compounds to see what worked.”
Drugs generally work by interacting with receptors on the surface of cells or enzymes in the body, which have a specific three-dimensional structure that requires a precise fit – like a lock and key. Once the drug has attached to its target receptor, this will usually trigger (or inhibit) some sort of chemical reaction, leading to the desired therapeutic effect.
Now, instead of drug discovery involving the arduous process of chemical trial and error, machines like the one at Diamond are heralding a new era of rational drug design. Scientists first identify the atomic structure and properties of their target, and then design drugs that fit the atomic lock and key, thereby carefully tailoring treatments to the specific qualities of that disease.
“This allows the creation of drugs which are more effective and have fewer side effects,” explains Harrison.
Such insights have already led to the development of antiviral treatments for HIV/AIDS. Other notable drugs that have come out of it are Tamiflu (a drug prescribed for flu infections – including H1N1, aka swine flu) and, more recently, a drug for Hepatitis C.
“Many drugs for cancer are also now derived from structure-based design,” he adds.
So aside from tailored designs and better effectiveness, how is synchrotron-assisted drug design a game changer?
Bringing new drugs to market is a lengthy and costly business, and new trends in rational drug design may make this process quicker and cheaper. In fact some companies have been formed with the sole purpose of designing drugs in this way. A research group recently determined the shape of a protein essential to the formation of the “cloak” used by bacteria to evade the immune system and protect against antibiotic compounds.
There are 24 beam lines at Diamond today, up from one beam line when it opened in 2007. A further nine beamlines are currently under construction, bringing the total to 33 by 2018. The machine can cater to up to 40 more, so it looks like moving ahead, we can expect more exciting developments from this remarkable piece of technology.
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