The click chemistry that won Morten Meldal, Barry Sharpless, and Carolyn Bertozzi this year’s Nobel Prize in Chemistry is about making difficult processes easier.
Click chemistry and bioorthogonal reactions — which take place without disrupting the normal functioning of the cell — have taken chemistry into the era of functionalism, bringing the greatest benefit to humankind.
Sharpless from Scripps Research, US, and Meldal from the University of Copenhagen, Denmark, laid the foundation for a functional form of chemistry in which molecular building blocks snap together quickly and efficiently.
Bertozzi, from Stanford University, US, took this click chemistry to a new dimension and started utilising it in living organisms.
Chemists have long been driven by the desire to build increasingly complicated molecules.
In pharmaceutical research, this has often involved artificially recreating natural molecules with medicinal properties. This has led to many admirable molecular constructions, but these are generally time consuming and very expensive to produce.
”This year’s Prize in Chemistry deals with not overcomplicating matters, instead working with what is easy and simple. Functional molecules can be built even by taking a straightforward route,” said Johan Aqvist, Chair of the Nobel Committee for Chemistry.
Sharpless, who is now being awarded his second Nobel Prize in Chemistry, started the ball rolling.
Around the year 2000, he coined the concept of click chemistry, which is a form of simple and reliable chemistry, where reactions occur quickly and unwanted by-products are avoided.
Shortly afterwards, Meldal and Sharpless — independently of each other — presented what is now the crown jewel of click chemistry: the copper catalysed azide-alkyne cycloaddition.
Azide is an organic compound with the formula N3 while an alkyne is a hydrocarbon containing at least one carbon-carbon triple bond.
This is an elegant and efficient chemical reaction that is now in widespread use. Among many other uses, it is utilised in the development of drugs, for mapping DNA and creating materials that are more fit for purpose. Bertozzi took click chemistry to a new level.
To map important but elusive biomolecules on the surface of cells — glycans — she developed click reactions that work inside living organisms.
These reactions are now used globally to explore cells and track biological processes.
Using bioorthogonal reactions, researchers have improved the targeting of cancer drugs, which are now being tested in clinical trials.