Nobel Prize for click chemistry: the molecular hobbyists

Nobel Prize for click chemistry: the molecular hobbyists

Nobel Prize for Click Chemistry
The Molecular Hobbyists

By Kai Stoppel

It is still a young technology, but already widespread: click chemistry. Their three discoverers and developers are awarded the Nobel Prize in Chemistry. Her pioneering work could also lead to new treatments for diseases in the future.

Sounds like a model building kit for kids: click chemistry. Simply put together, done. And for something similar, three researchers have now been awarded the Nobel Prize in Chemistry. They developed ways to assemble biomolecules as easily as desired.

The 68-year-old Morten Meldal from Denmark and the 81-year-old Barry Sharpless from the US are considered the pioneers of so-called click chemistry. This is Sharpless’s second Nobel Prize, making him one of only five people to have won it. Finally, 56-year-old American Carolyn Bertozzi of the American University of Stanford resolutely further developed click chemistry and applied it to living organisms. She is only the eighth woman to receive a Nobel Prize.

Chemists have been able to assemble biomolecules for quite some time – but this often requires many steps. And each step can make the process more inefficient. Chemists often achieve their challenging goals, but the journey can be both time-consuming and expensive. The researchers’ work “spurred a revolution in the way chemists think about connecting molecules.”

“Almost As It Sounds”

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Click chemistry “has revolutionized the way we can analyze or see molecules in the living body,” said Olof Ramstrom, a member of the Nobel Committee.

(Photo: IMAGO/TT)

Click chemistry uses existing carbon frameworks. “Click chemistry is almost what it sounds like,” Johan Åqvist, chairman of the Nobel Committee for Chemistry, said announcing the decision. “Imagine that you could attach small chemical buckles to different types of building blocks. Then you could connect those buckles together to create molecules of greater complexity and variety.” It’s like a backpack buckle where one piece fits snugly into the other. Once it “clicks”, the connection is solid. The three researchers managed to make these buckles.

Sharpless was the first to come up with the idea of ​​pluggable molecules. Almost simultaneously, but independently of him, the Dane Meldal presented the first click reaction in 2002, turning the idea into reality. “When this reaction was discovered, it was like opening the floodgates,” Olof Ramstrom, a member of the Nobel Committee on Chemistry, said in a briefing after the prize winners were announced. “We’ve used them everywhere to build everything.”

However, the principle of Meldal and Sharpless uses copper, which is harmful to the human body. Bertozzi improved the click technology and omitted the toxic copper ions. The practicality: thanks to further development, certain processes in the body that researchers had previously hidden could be made visible. Because thanks to the click technique, Bertozzi was able to attach dyes to sugar chains on the surface of cells. Their work “has revolutionized the way we can analyze or see molecules in the living body,” Ramstrom said.

“Click chemistry still in its infancy”

For example, the bioorthogonal marking developed by Bertozzi is currently used in cancer therapies. In cancer medicine, a specific antibody finds a tumor cell. In a second step, a molecule that can destroy the cancer cell, for example, binds to the antibody via a click reaction.

“The field of click chemistry is still in its infancy,” Bertozzi told the New York Times after the Nobel Prize announcement. She added that there were “a lot of new reactions to explore and find out.” Nobel Committee Chairman Aqvist noted that click chemistry is now being used “to build drug molecules, polymers, new materials, and many other things.”

The two award-winning methods have “long established themselves in the toolset of biomedical and pharmaceutical companies and institutions,” according to the Association of Research-Based Pharmaceutical Companies (vfa). Click chemistry is now standard in many research laboratories. As Aubry Miller, head of the drug discovery group at the German Cancer Research Center, puts it, “At chemical biology conferences, every lecture has something to do with click chemistry.”

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