A toolkit for assembling molecules like Lego building blocks has won the Nobel Prize in Chemistry 2022.
Chemists Carolyn Bertozzi of Stanford University, Morten Meldal of the University of Copenhagen, and Barry Sharpless of the Scripps Research Institute in La Jolla, California, will split the prize equally for developing click chemistry and bioorthogonal chemistry, the Royal Swedish Academy announced. Science in October. 5 at a press conference in Stockholm. These tools allow scientists to easily build complex molecules in the laboratory and within living organisms.
“The beauty of this discovery is that it can be used for almost anything,” said Olof Ramström, a chemist at the University of Massachusetts Lowell and a member of the Nobel committee for chemistry. Applications include the construction of drug molecules, polymers, new materials, and the tracking of biomolecules between cells.
“We are already at the tip of the iceberg in terms of applications,” says Angela Wilson, president of the American Chemical Society. “I think this chemistry is going to revolutionize medicine in many areas.”
About 20 years ago, Sharpless introduced “click chemistry,” a way to simply and quickly join two compounds together using certain linker molecules. But finding these Lego-like connecting molecules that can come together in a chemical reaction wasn’t easy. Working independently, Sharpless and Meldal discovered a solution.
By adding a pinch of copper to a mixture containing two other small molecules, called an azide and an alkyne, the scientists were able to quickly bind the two molecules together into a ring-shaped chemical. Without the copper, the molecules would eventually combine, but slowly, Ramström said.
The reaction quickly “gained enormous interest in chemistry and related fields,” he added. Although scientists would go on to discover a handful of other molecules that could bind in the same way, that first reaction is considered the “crown jewel of click reactions.”
But while catalyzing reactions with copper can work fine in a beaker, the metal can damage living cells. Bertozzi discovered a way to do click chemistry without copper, so scientists can now engineer chemical reactions inside organisms without disrupting their normal cellular functions.
Bertozzi tricked cells into incorporating a chemical click into the sugars that decorate the cell’s surface. When scientists expose these cells to a different click chemical, a type of alkyne, the two can bond, much like the molecules in the Sharpless and Meldal reactions. By linking the alkyne to bright green molecules, scientists can illuminate cell surfaces.
“Imagine if you could attach glowing molecules to biomolecules in a living cell. You could then follow them under a microscope and see where they are and how they move. This is what Carolyn Bertozzi did.” said Johan Åqvist, a theoretical chemist at Uppsala University in Sweden and chairman of the Nobel committee for chemistry.
Bertozzi’s specialty has been the study of sugar molecules, which “are incredibly difficult to work with,” says Leslie Vosshall, a neuroscientist at Rockefeller University in New York City who is vice president and chief scientific officer of the Howard Medical Institute. Hughes. There are easy methods to look at DNA, RNA and proteins, but not so much for sugars, she says. “Sugars are the dark matter of the cell.”
By targeting specific sugars on cell surfaces, scientists can develop new treatments. For example, Bertozzi and his colleagues were able target and disable sugars that were helping tumor cells hide from T cells in the body (Serial number: 03/21/17).
Bertozzi, an HHMI investigator, is the 59th woman to win a Nobel Prize since 1901, and only the eighth to receive a prize in chemistry. In 2021, Emmanuelle Charpentier and Jennifer Doudna were the last women to win the Nobel Prize for Chemistry, for their work on the gene editing tool known as CRISPR (7/10/21).
“Carolyn is… one of the surprisingly few women in chemical biology,” says Vosshall. “His lab of hers has been a generative place that has inspired women chemists and put them out there in the world.”
Waking up to the news around 3 a.m. PT, Bertozzi said, “I am absolutely stunned. I’m sitting here and I can hardly breathe.” To say that the phone call in the middle of the night was a shock is an understatement, he added. “I’m still not entirely sure it’s real, but it’s getting more real by the minute.”
Bertozzi, Meldal and Sharpless will share the prize: 10 million Swedish kronor, approximately $917,000. The prize is the second Nobel for Sharpless, who shared the prize in 2001 for her work on development of catalysts for oxidation reactions.