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The Nobel Prize to click chemistry

The Nobel Prize to click chemistry
© Nobel Prize Outreach. Ill. Niklas Elmehed

The Nobel Prize to click chemistry

14 October, 2022

The 2022 Nobel Prize in Chemistry has been awarded to Carolyn Bertozzi, Morten Meldal and Barry Sharpless, for their research in click chemistry and bioorthogonal chemistry – areas that have received wide practical application. Click chemistry means that through smaller building blocks, you can design large, complicated molecules for, for example, the development of new materials. Bioortogonal reactions are based on the principles of click chemistry but can be used in living cells, which has become important for the development of new drugs.

For the second time, the American scientist K Barry Sharpless will receive the Nobel Prize in Chemistry. The last time, in 2001, Sharpless was awarded for the work behind chirally catalysed oxidation reactions, which have been applied in, among other industries, the pharmaceutical industry. This time he receives the prize together with Danish Morten Meldal and American Carolyn Bertozzi for the research on click chemistry and bioorthogonal reactions.

Prized click chemistry

Around the turn of the century, Sharpless coined the term click chemistry for a method in which molecular building blocks click into each other to create larger molecules in quick reactions with no by-products. Previously, complicated molecular construction was associated with long development times and extensive material waste.

The solution to the problem was to start from smaller units and Sharpless and Meldal developed, independently of each other, the copper-catalyzed azide-alkyne cycloaddition. Very simplified, you can describe the discovery as follows: if you want to connect two different molecules, you can relatively easily insert an azide into one molecule and an alkyne into the other and then snap them together with the help of copper ions.

This creates an effective chemical reaction that has been widely disseminated by chemists, allowing them to create new suitable materials that can, for example, be antibacterial or electrically conductive, or that can capture sunlight.

Bioorthogonal reactions yields new drugs

Sharpless and Meldal share the prize with Bertozzi, who in her research has exploited the advantages of click chemistry in biochemistry. In the mapping of biomolecules on the surface of cells, glycans, Bertozzi developed the strain-promoted azide-alkyne cycloaddition, a method that uses the principles behind click chemistry but without the toxic copper. The method can thus be used in living organisms without interfering with the normal chemistry of the cells, Bertozzi chose to call this bioorthogonal chemistry.

With the help of Bertozzi’s discovery, chemists have been able to study how biomolecules and cells interact in different disease processes, including cancer. One example is how glycans on the surface of tumour cells can protect the tumours from the body’s immune system. In the development of new biological drugs, they are now trying to combine an antibody that binds to the tumour and at the same time has tumour-killing properties linked to it. This approach is currently being tested in clinical studies in advanced cancer, but we are still awaiting the results.

Elegant, clever, novel and useful

When Sharpless received his first Nobel prize he used four words to describe his ideals when it came to chemistry– elegant, clever, novel and useful. There is no doubt that these words can be applied to the development of click chemistry and bioorthogonal reactions. These have become established methods that have given chemists opportunities to improve material development and treatments of severe diseases. For these elegant and useful discoveries and their applications, Bertozzi, Meldal and Sharpless now have the opportunity to travel to Stockholm in December to receive prizes and diplomas from the king’s hand.

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