Nobel Prize awarded to three scientists for their work on the chemistry of the click, which quickly connects molecules

The 2022 Nobel Prize in Chemistry has been awarded to three scientists for their work in a field known as click chemistry, which allows molecular building blocks like LEGO pieces to be put together to create complex molecules with huge implications for pharmaceutical development, medicine and materials science.

The prize was awarded to two Americans, K. Barry Sharpless of Scripps Research in La Jolla, California, and Carolyn R. Bertozzi of Stanford University, and Danish scientist Morten Meldal of the University of Copenhagen.

Sharpless and Meldal developed the field of click chemistry in which molecular building blocks are linked quickly and efficiently. Bertozzi built on these advances to develop bioorthogonal chemistry, which allows scientists to modify molecules in living organisms without disrupting processes occurring in cells – a technique that enables cell mapping and targeted therapies against the cancer, among other uses.

“I am absolutely amazed,” Bertozzi said early this morning when she was woken at her home in Palo Alto by the call from the Nobel committee. “I’m sitting here and I can barely breathe. I’m still not quite sure if it’s real.

Later, in an interview with The Washington Post, Bertozzi said that as soon as she picked up that call, she phoned her father, William Bertozzi, 91, a former professor of physics at the Massachusetts Institute of Technology.

“Dad,” she said, “you won’t believe this but I just got a phone call.”

When she stopped, he exclaimed, “Oh my God, you won the Nobel Prize.”

Johan Aqvist, chairman of the Nobel Committee for Chemistry, praised the three scientists for simplifying extraordinarily complicated processes.

“Click chemistry is almost how it sounds,” he said at the Stockholm briefing. “It’s about slamming molecules together. Imagine being able to attach small chemical loops to different types of building blocks. Then you could link those loops together and produce more complex and varied molecules. This was the basic idea that Barry Sharpless had about 20 years ago. The problem was finding good chemical loops.

Scientists solved this problem in stages, he said. Sharpless and Meldal’s research – conducted independently of each other – used copper as a catalyst to bind molecules together, which was effective but toxic at higher concentrations. Bertozzi has developed a method that allows scientists to modify molecules in living organisms without disrupting them.

“It’s an excellent choice. It’s really elegant chemistry,” said former National Institutes of Health director Francis S. Collins. Click chemistry improves tumor targeting of cancer drugs, he said, some of which are currently in clinical trials.

Jon Lorsch, director of the National Institute of General Medical Sciences at the National Institutes of Health, likened Bertozzi’s method to a trap that closes once the animal is inside. “When the partner molecule enters, it closes and only acts on the partner molecule.”

The work of the laureates has already found “a large number of applications. It is used to assemble molecules of different sizes to create huge [chemical] libraries that can be used to screen for drugs,” said Lorsch. The method also allows scientists to attach a dye to a molecule and watch where it goes and what it does, such as when a virus infects a cell.

The concept of click chemistry has been “transformative” in many fields of chemistry, materials science, biology and medicine, said Tom Brown, professor of nucleic acid chemistry at the University of Oxford. “He gave rise to highly functional new materials, catalyzed important pharmaceutical developments, and had an influence in many areas of chemical biology.”

The research recognized by the award spans at least two decades, but “in many ways this is still technology that is still in its infancy,” said Angela K. Wilson, president of the ‘American Chemical Society. “We talk a lot about personalized medicine and I think that’s going to help open doors for that in the future.”

Wilson said the techniques used to link the molecules should also have applications for regrowing damaged tissue and for reading the genetic script of humans, animals and plants.

They also have industrial applications, including developing ways to prevent corrosion and brighteners used to make plastics and other materials cleaner, she said.

Bertozzi. who also won a “Genius” MacArthur Award at 33, is the third woman to win the chemistry prize in as many years. In 2020, the Academy recognized Jennifer A. Doudna from the University of California, Berkeley and Emmanuelle Charpentier from the Max Planck Research Unit for Pathogen Science in Berlin, for developing the editing tool of the genome known as CRISPR/Cas9.

“Many years ago, chemistry, like many fields, was male dominated,” Wilson said. “There are a lot more women in the field and they are doing amazing science,” Wilson said, noting that pioneering chemist Marie Curie was the first person to receive two Nobel Prizes.

Sharpless, 81, became the fifth person to win a second prize, joining Curie and Frederick Sanger, the only other person to win the chemistry prize twice. Sharpless previously won in 2001 “for his work on chirality-catalyzed oxidation reactions,” a process that has enabled the manufacture of antibiotics, anti-inflammatories, heart medications and more agricultural chemicals. safer and more effective.

“He’s going in his own direction,” said Miles Fabian, program manager at the National Institute of General Medical Sciences, of what sets Sharpless apart as a scientist. “He always had a good idea of ​​what is needed in chemistry.”

Michelle Bond, another NIGMS program manager, said Bertozzi “is one of the reasons I went to graduate school. Not only is she an excellent chemist, but she’s incredibly good at communicating to the public the importance of [her work] and its future potential.

Bertozzi’s work advanced the field of glycoscience, which focuses on carbohydrates on the surface of virtually every cell involved in linking and communicating with other cells.

These carbohydrates differ when the cells are healthy or diseased. Identifying these differences allows researchers to target diseased cells. Glycoscience has proven important to our understanding of cancer, inflammation, diabetes, heart disease, and even covid-19.

Bertozzi told the Post that Shasqui, a San Francisco-based biotech company, is already conducting a Phase 2 clinical trial using the chemistry it developed to treat patients with solid tumors that have reached an advanced stage at a location or have spread to other areas of the body.

“We are encouraged by the promising results,” company CEO José M. Mejía Oneto said in a press release. Press release last month announcing the phase 2 study.

Bertozzi said she is also the founder of three companies working on practical applications of her findings: Palleon Pharmaceuticals in Waltham, Mass. ; Lycia Therapeutics in San Francisco; and Redwood Bioscience SMARTag in Emeryville, California.

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