Nobel Prize for Click Chemistry: Molecules based on the Lego principle

Status: 05.10.2022 17:37

Medicines, plastics or other complex molecules – their production was complex and expensive for a long time. Click chemistry has radically simplified many of these processes — with a clever trick.

By Vinetta Richter, Ralf Kölbel and Nina Kunze, science editors of SWR

Millions of medicines are needed worldwide every day. However, its manufacture, like many other everyday materials, often requires very complex molecules. These are often difficult to produce, for example because the process is energy-intensive and expensive or because unwanted by-products are created. Carolyn Bertozzi and K. Barry Sharpless from the US and the Dane Morten Meldal developed mechanisms that simplify this process: click chemistry. This makes it possible to quickly and deliberately assemble molecules from smaller units, similar to what nature does.

Assemble molecules like Lego bricks

Sharpless and Meldal independently made a similar discovery about 20 years ago. It works in the same way as Lego blocks that are clicked together: you take two molecules and give them a so-called functional group, in this case the Lego blocks.

Meldal also found that the click process is much more efficient if you add a certain substance, in this case copper. The molecules react faster with each other, it “clicks” and a connection is formed. There are now many other ways to create such a click connection.

Nobel Prize in Chemistry awarded to three molecular researchers

Christian Blenker, ARD Stockholm, daily news at 14:00, October 5, 2022

Use in living organisms

The biochemist Bertozzi further developed the technology so that it can also be applied in living cells. Specifically, she found a way to make click connections in living organisms without copper – because copper is dangerous for human cells. The process is called “bioorthogonal reaction”. It is a chemical reaction that can take place within living systems without disrupting other processes.

This method is already used worldwide to study cells and monitor biological processes. Researchers have also improved the targeting of cancer drugs being tested in clinical trials. “The field of click chemistry is still in its infancy,” Bertozzi said in a conference call following the Nobel Prize announcement, adding that “there are many new reactions to be discovered and invented.”

The application areas are diverse

For example, the processes of click chemistry are used in the pharmaceutical industry, as the chemist Thomas Brück of the Technical University of Munich talks to tagesschau24 explained. A specific field of application is the search for new antibiotics. “We can mark potential new substances with a glowing molecule and then track where they work in the cell. You can then say, for example, that this molecule binds to this protein or to this ingredient in the cell. this molecule continues to evolve into a new active ingredient that helps us defeat bacterial diseases.”

Conversely, it is also possible to observe where bacteria attack human cells. “Patients often bind to special sugar molecules on the cell surface. With a marker there, we can track the disease progression in real time and determine exactly where the pathogens bind and how they do it. And that gives us information on how we can design new active pharmaceutical ingredients. “

Thomas Brück, Technical University of Munich, on the Nobel Prize in Chemistry for three molecular researchers

tagesschau24 12 noon, 5.10.2022

There are many different ways to use the click method. For example, in the development of new materials. It is possible to determine in advance which properties the new material should have.

“Light on Chemical Biology”

Sharpless has achieved something special with this prize: it is already his second Nobel Prize. In 2001 he was honored with the coveted knowledge prize for his work on oxidation reactions. Only a few have managed to do this for him, including the physicist and chemist Marie Curie.

For Bertozzi it is the first Nobel Prize – this was also reflected in their reactions. “I’m absolutely stunned. I’m sitting here and I can barely breathe,” she said after the announcement. “I’m still not quite sure if it’s real, but it’s getting more real by the minute.” While she says she hasn’t had time to think about how the prize money will be used, she has already stressed that the prize “sheds light on chemical biology, is a great thing.”

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