Bioorthogonal reactions – doing chemistry inside living cells without blasting everything in sight – are no mean feat
When we do chemical reactions, it’s normally done under extremely controlled conditions. Whether it’s in a Schlenk tube, a round-bottomed flask or a plant-scale reaction vessel – we only add exactly what we want: reactants, reagents and a solvent if required. Water and air can be excluded from the system if they would interfere with the carefully choreographed chemistry.
Now imagine trying to perform this kind of precise chemistry – tweaking this functional group on that molecule just so, while leaving everything else untouched – in a living cell. In a reaction vessel that is chock full of water and a messy mix of compounds, all bristling with different functional groups, how do you attach a label to a specific biomolecule, for example, without labelling everything else in there?
That’s exactly what bioorthogonal chemistry does. And its success means it is easy to see why Carolyn Bertozzi of the University of Stanford in the US, who is widely credited with kickstarting the field around 20 years ago, is regularly on people’s shortlist for a future Nobel prize.
Bioorthogonal chemistry mostly uses a range of different click reactions – fast, effective coupling between specific functional groups – to attach probes to biomolecules so we can learn more about the inner workings of cells. But it doesn’t stop at probes. As James Mitchell Crow writes in his feature, the techniques have been adapted to help drugs find their targets. This could make them more effective and mean patients have to take less of them, an important consideration for many drugs with unpleasant side-effects.
It’s a textbook example of something that was perhaps originally only expected to be useful in a research lab or chemical plant – the Huisgen 1,3-dipolar cycloaddition, for example – going on to have profoundly important implications in areas beyond what its inventors could have imagined.
It’s inspiring to think that such classic tools from the synthetic chemist’s toolkit can be used to such a great interdisciplinary effect. Where will the compounds or reactions you study in the lab today end up?