Nobel prize in chemistry awarded for reliable molecule-building tool

The 2022 Nobel prize for chemistry has been jointly awarded to Carolyn Bertozzi, Morten Meldal and K. Barry Sharpless for the development of click chemistry – linking molecules together – and bioorthogonal chemistry, which allows such reactions to happen in living cells.

“Click chemistry is chemistry based on specific reactions that work very efficiently and are very reliable to generate robust yields of products,” said Olof Ramström, a member of the Nobel Committee, during the announcement. “You can essentially snap together two molecule building blocks in a very efficient and predictive way to get a lot of product.” 

“Click chemistry has applications in pharmaceutical development, in DNA sequencing… and in the production of new materials,” he said. “Bioorthogonal reactions have helped with exploring the roles of biomolecules in cells and organisms, have helped with deciphering disease processes, and of course that can lead to the development of new drugs.”

Sharpless, along with his team, first proposed the idea of click chemistry in 2001. From 2001 to 2002, Meldal and Sharpless worked in groups that independently discovered that copper ions could be used to kick-start a reaction between a molecule called azide and another molecule called alkyne.

“[This was] the crown-jewel of click reactions,” said Ramström.

A few years later, in 2004, Bertozzi and her colleagues pioneered click reactions that didn’t require copper. Too much metal can be toxic to living cells, so this change meant metal-free reactions could be made to occur inside cells without interfering with other aspects of cell metabolism.

Such reactions eventually allowed Bertozzi to label molecules found on cell surfaces, called glycans, with fluorescent green tags. This helped to reveal that some glycan molecules found on cancer cells help to protect them from the immune system. Bertozzi and her colleagues then developed a new type of antibody – now being tested in clinical trials – that can guide enzymes to break down glycans on the surface of tumour cells, exposing them to the immune system.

Other researchers are using “clickable antibodies” to help target lethal doses of radiation to tumour cells.

“I am absolutely stunned. I’m sitting here and can hardly breathe. I’m still not entirely positive it’s real but it’s getting realer by the minute,” said Bertozzi in response to the news she had won.