The 2022 Nobel Prize in Chemistry was awarded for a method of joining molecules using a "Lego-like" system of "clicks."

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• biomolecules
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• bioorthogonal

There are three scientists widely credited as the creators of both "click chemistry" and "bioorthogonal chemistry."

The chemistry Nobel Prize for 2022 went to a set of tools for assembling molecules like Lego bricks.

The Royal Swedish Academy of Sciences made the announcement at a press conference on October 5 in Stockholm that the prize for developing click chemistry and bioorthogonal chemistry would be shared equally by 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. With the help of these devices, scientists can readily build complicated chemicals in the lab and even within live beings.

Olof Ramström, a chemist at the University of Massachusetts Lowell and member of the Nobel committee for chemistry, said, "The nice thing about this discovery is that it may be utilized for nearly anything." Drug design, polymer synthesis, material innovation, and intracellular monitoring of biomolecules are just few of the many potential uses.

When it comes to potential uses, "we're sort of at the tip of the iceberg already," says Angela Wilson, president of the American Chemical Society. It's my opinion that "this chemistry will change the face of medicine in so many ways."

It was around 20 years ago that Sharpless created "click chemistry," a method of swiftly and easily joining two chemicals using certain connector molecules. It wasn't simple to identify molecules that might behave as "lego-like connectors" in a process. Sharpless and Meldal, working separately, came up with a solution.

Scientists were able to quickly snap together two tiny molecules into a ring-shaped compound by adding a trace amount of copper to a mixture containing two additional small molecules, known as an azide and an alkyne. Ramström claimed that the molecules would mix without the copper, although slowly.

Fast, he said, the reaction "gained significant attention in chemistry and related areas." The first reaction of its kind is celebrated as the "crown gem of click reactions," despite the subsequent discovery of a few more compounds that might snap together in a similar method.

While copper may be used to catalyze processes in a glass beaker, it should not be used near live organisms due to the metal's toxic effects on their DNA. Bertozzi found a means to do click chemistry without the need of copper, allowing scientists to create chemical reactions inside animals without disrupting normal biological functioning.

Bertozzi fooled the cells into adding a click chemical to the sugars that decorate the cell's surface. Similar to the molecules in the reactions of Sharpless and Meldal, when scientists subject these cells to a different click chemical, a sort of alkyne, the two may snap together. Scientists can shine light on cell surfaces by joining the alkyne to molecules that glow green.

Let's say you have the ability to affix fluorescent molecules to biomolecules in a live cell. The microscopical tracking of their whereabouts and behaviors would then be possible. According to Johan qvist, a theoretical chemist at Uppsala University in Sweden and the head of the Nobel committee for chemistry, this is exactly what Carolyn Bertozzi performed.

Researching sugar molecules, which "are exceedingly tough to deal with," has been Bertozzi's focus, according to Leslie Vosshall, a neurologist at New York's Rockefeller University and the vice president and chief scientific officer of the Howard Hughes Medical Institute. Straightforward tools exist for looking at DNA, RNA and proteins, but not so much for sugars, she adds. In a cell, sugars serve as a kind of "dark matter."

Scientists may find novel medicines by focusing on certain sugars found on cell surfaces. For instance, Bertozzi and coworkers were able to zero in on and disable carbohydrates that tumor cells used to evade the body's T cells (SN: 3/21/17).

The HHMI researcher, Bertozzi, is just the seventh woman to receive the Nobel Prize in chemistry since 1901. The latest women to receive a Nobel Prize in chemistry were Emmanuelle Charpentier and Jennifer Doudna, who did so in 2021 for their work on the CRISPR gene-editing technology (10/7/21).

Vosshall remarks, "Carolyn is... one of the startlingly few women in chemical biology." As one reviewer put it, "her lab has been a generative site that has inspired women chemists and sent them out into the world."

Bertozzi stated, "I'm utterly startled" when he heard the news at 3 a.m. Pacific Time. Sitting here, I feel like I have no air in my lungs. To say that the call in the middle of the night came as a surprise would be an understatement, she said. "I'm not quite certain that it's genuine, but it seems more and more plausible by the second."

CITATIONS

Nobelprize.org. The Nobel Prize in chemistry 2022. Published online October 5, 2022.