Nobel Prize for 3 chemists who made molecules ‘click’

STOCKHOLM Three scientists were jointly awarded this year’s Nobel Prize in chemistry on Wednesday for developing a way of “snapping molecules together” that can be used to design better medicines, including ones that target diseases such as cancer more precisely.

Americans Carolyn R. Bertozzi and K. Barry Sharpless and Danish scientist Morten Meldal were cited for their work on click chemistry and bio-orthogonal reactions, which are used to make cancer drugs, map DNA and create materials that are tailored to a specific purpose.

“It’s all about snapping molecules together,” said Johan Aqvist, a member of the Royal Swedish Academy of Sciences that announced the winners at the Karolinska Institute in Stockholm.

Sharpless, 81, who previously won a Nobel Prize in 2001 and is now the fifth person to receive the award twice, first proposed the idea of connecting molecules using chemical “buckles” around the turn of the millennium, Aqvist said.

“The problem was to find good chemical buckles,” he said. “They have to react with each other easily and specifically.”

Meldal, 68, based at the University of Copenhagen, and Sharpless, who is affiliated with Scripps Research in California, independently found the first such candidates that would easily snap together with each other but not with other molecules, leading to applications in the manufacture of medicines and polymers.

Bertozzi, 55, who is based at Stanford University, “took click chemistry to a new level,” the Nobel panel said.

She found a way to make the process work inside living organisms without disrupting them, establishing a new method known as bio-orthogonal reactions. Such reactions are now used to explore cells, track biological processes and design drugs that can target diseases such as cancer more precisely.

“Doing chemistry inside human patients to make sure that drugs go to the right place and stay away from the wrong place,” Bertozzi explained.

Speaking by phone at a news conference following the announcement, Bertozzi said she was “absolutely stunned” to receive the prize.

Speaking to The Associated Press by Zoom, Bertozzi said one of the first people she called after being wakened by the call around 2 a.m. was her father, William Bertozzi, a retired physicist who was still awake watching TV.

“Dad, turn down the TV, I have something to tell you,” she said she told him. After assuring him nothing was wrong, he guessed the news. “You won it, didn’t you?”

One of three daughters, Bertozzi said she was “fortunate because I grew up with parents that were very supportive, evangelical almost, about having their girls participate in the sciences.”

Bertozzi said she was grateful for the energy and enthusiasm that a Nobel Prize win will inject into the field.

Meldal said he received the call from the Nobel panel about half an hour before the public announcement. “They … told me not to tell anyone,” he told the AP, adding that he just sat in his office, shaking a bit. “This is a huge honor.”

Meldal started out as an engineer, “but I wanted to understand the world, so I thought chemistry would give me the solutions.”

Jon Lorsch, director of the U.S. National Institute of General Medical Sciences, which supports the work of Bertozzi and Sharpless, described click chemistry and bio-orthagonal chemistry as “sort of like molecular Lego – you have a group on one molecule that specifically attaches to a group on another molecule,” like Legos clicking together.

“That makes it possible to attach molecules in very specific pre-defined ways,” he said, and gives scientists a very precise tool to build complex new molecules that can be used for drugs, synthetic materials and other uses.

However, the first iteration of click chemistry could not initially be used to work on living cells.

“The original click chemistry used copper as a catalyst to join molecules,” Lorsch said. “But the trouble is that copper is toxic to most living systems at higher concentrations.”

Bertozzi then devised a way to jumpstart the reactions without copper or other toxic solvents – broadening the applications of the molecular Lego to human and animal tissues.

“Being able to work without dangerous solvents opened many news doors – it enabled scientists to work on new types of reactions that actually take place within the human body,” said Angela Wilson, president of the American Chemical Society.

For example, that work has allowed scientists to attach dyes to cancer cells to track their movements and analyze how they differ from healthy tissue.

Wilson believes that the advances of this year’s Nobel laureates “will allow more individualized medicine in the future because we can really track things much better within the human body.”

The prizes carry a cash award of 10 million Swedish kronor (nearly $900,000) and will be handed out on Dec. 10. The money comes from a bequest left by the prize’s creator, Swedish inventor Alfred Nobel, in 1895.

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