A tool kit for snapping together molecules like Lego blocks has won the 2022 Nobel Prize in chemistry. Chemists Carolyn Bertozzi of Stanford University, Morten Meldal of the University of Copenhagen and Barry Sharpless of the Scripps Research Institute in La Jolla, Calif., will evenly split the prize for developing click chemistry and bioorthogonal chemistry.
These tools allow scientists to easily construct complex molecules in the lab and inside living organisms.
“The good thing with this discovery is that it can be used for almost everything,” said Olof Ramström, a chemist at the University of Massachusetts Lowell and a member of the Nobel committee for chemistry. Applications include building drug molecules, polymers, new materials and tracking biomolecules among cells.
“We’re kind of at the tip of the iceberg already in terms of applications,” says Angela Wilson, president of the American Chemical Society. “I think this chemistry is going to revolutionize medicine in so many areas.”
Around 20 years ago, Sharpless introduced “click chemistry” — a way to simply and quickly attach two compounds using certain connector molecules. But finding these Lego-like connector molecules that can bond together in a chemical reaction wasn’t easy. Working independently, Sharpless and Meldal discovered a solution.
By adding a smidge of copper to a mixture containing two other small molecules — called an azide and an alkyne — the scientists could rapidly snap the two molecules together into a ring-shaped chemical. Without the copper, the molecules would eventually combine, but sluggishly, Ramström said.
The reaction quickly “gained enormous interest across chemistry and related fields,” he added. Even though scientists would later discover a handful of other molecules that could snap together in the same fashion, that first reaction is considered the “crown jewel of click reactions.”
But while catalyzing reactions with copper may work fine in a glass beaker, the metal can harm living cells. Bertozzi discovered a way to do copper-free click chemistry, so scientists can now design chemical reactions inside of organisms without mucking up their normal cellular functions.
Bertozzi tricked cells into incorporating a click chemical into sugars decorating the cell’s surface. When scientists expose these cells to a different click chemical, a type of alkyne, the two can snap together, just like the molecules in Sharpless’ and Meldal’s reactions. By linking the alkyne to green-glowing molecules, scientists can illuminate the surfaces of cells.
By incorporating Lego-like chemicals into sugars on the cell surface, scientists can snap on green-glowing or other molecules to track specific cells. Here, large surface proteins with chains of sugars (illustrated, yellow) are shown on the outside of a cancer cell.
