2022 The Nobel Prize in Chemistry was jointly awarded to three researchers: Carolyn Bertozzi for her development of bioorthogonal chemistry, and Morten Meldal and K. Barry Sharpless for their independent development of click chemistry
Carolyn Bertozzi, Morten Meldal and K. Barry Sharpless for her 2022 Nobel Prize in Chemistry for click chemistry and bioorthogonal chemistry. Click chemistry revolutionizes the options chemists can use to create desired molecules. Bioorthogonal chemistry makes it possible to monitor chemical processes that occur inside living cells without damaging them. "It's all about adsorbing molecules together," said Johan Åqvist, chairman of the Nobel Committee on Chemistry, on the announcement. Imagine he told the audience that you could attach small chemical buckles to a bunch of different types of molecular components and then connect these buckles together to create complex molecules. The idea came up with Barry Sharpless of the Scripps Institute about 20 years ago, and later became a reality when he and Morten Meldal of the University of Copenhagen found the first perfect candidates independently. Their buckles are easy to buckle together and won't attach to anything that shouldn't be attached.
Then, in 2003, Carolyn Bertozzi proposed that click chemistry could be used in the study of biological systems so that important cellular processes can be observed more easily without disturbing them. Bertozzi called this "bioorthogonal" chemistry in a paper published by her and her colleagues that year. Since then, the term has been widely adopted in this field.
's ability to perform complex reactions in a living system without interfering with natural biological reactions makes it possible to study molecular and cellular processes in complex organisms such as cells and zebrafish, rather than in laboratory dishes. It has helped scientists understand an important protein processing reaction called glycosylation, helping to develop molecular imaging molecules that can detect diseases of organisms, and opening up the possibility of selective delivery of drugs to specific tissues in the body. The findings “caused a revolution about how chemists think about connecting molecules together and how to connect them in living cells,” said
Åqvist.
Today's announcement marks Sharples' second Nobel Prize in Chemistry. In 2001, he won awards with William Knowles and Ryoji Noyori for the development of catalytic asymmetric synthesis.
What is click chemistry?
Sharpless For most of the 1990s, it was considered whether it was necessary to find an easier way to synthesize complex molecules. His ideas peaked in a 2001 paper where he and his co-authors proposed the term “click chemistry” to refer to any reaction that links molecular building blocks together in an efficient, concrete and rapid way. Shortly after the paper was published, Meldal and Sharpless independently discovered the first click chemistry: a very useful reaction called copper-catalyzed azide-alkyne cycloaddition reaction. On one side of the reaction is an azide, a molecule with three continuous nitrogen atoms. On the other side is an alkyne, a molecule in which two carbon atoms are bonded together by triple bonds. By itself, the two building blocks are not very reactive: they react slowly and produce a mixture. But Meldal and Sharpless respectively realized that if they added a little copper to the mixture, the reaction accelerated sharply and mainly produced a stable product called triazole.
By strategically adding azide and alkyne "tags" into the molecules, chemists can use this copper catalytic reaction to precisely link them into larger molecules with specific structures.
Oloframstrom of the Nobel Committee said in an announcement that the copper-catalyzed reaction immediately aroused "huge interest" in chemistry and related fields.Although other click chemistry reactions have been found, “this particular reaction has become almost synonymous with the concept of click chemistry, often also known as the click reaction,” Ramström said. "You can say it's still the crown jewel of click reaction."
What is bioorthogonal chemistry?
In 2003, Bertozzi coined the term “bioorthogonal chemistry” to refer to any type of chemical reaction that may occur in a living system without disturbing or harming it. It is click chemistry that can be applied to living organisms. The seeds of the idea of
were germinated in the 1990s, when Bertozzi began to study a specific glycan, the complex sugar found on the cell surface. It was not easy to study this glycan using the chemical techniques she had available at the time. But after hearing another scientist hosting a workshop on inducing cells to produce non-natural sugar molecules, Bertozzi was inspired to consider whether she could do something similar to map the glycans on the cells. That was when she started studying bioorthogonal chemistry.
How is bioorthogonal chemistry used to study life systems?
Bertozzi came up with an easy way to track glycans on cells. First, she cultured cells near the modified sugar attached to the azide. The cells absorb the modified sugar and incorporate it into the glycan on their surface. Bertozzi then added an alkyne to the mixture, which had a fluorescent molecule attached to it. The alkynes react with the modified sugar and attach the fluorescent molecules to it. Through this simple reaction, the glycans emit green light, which allows Bertozzi to track their movements on the cell membrane under a microscope.
Today, Stanford University professor Bertozzi tracks glycans found on the surface of tumor cells. This work has led her to discover that certain glycans can protect tumor cells from the body's immune system. Her findings have opened the way for cancer immunotherapy, with many researchers working to find "clickable" antibodies against different types of tumors. Bertozzi and her team are also working on this issue. They have created a new drug that is currently in clinical trials. What other applications are there for glycan
click chemistry and bioorthogonal chemistry that targets and destroys the surface of tumor cells?
tracking molecules through and across cells is just one of many applications of click chemistry and bioorthogonal chemistry.
A major advantage of these techniques is that they do not introduce unwanted by-products into the reaction mixture—they are clean-efficient, allowing scientists to carefully craft complex molecules for a variety of purposes. Click chemistry has made great progress in drug development, DNA sequencing, synthesis of “smart” materials, and nearly every other application that chemists need to simply connect paired building blocks, said
Ramström. Researchers can now easily add functionality to a variety of materials, such as chemical expansions that can conduct electricity or capture sunlight by clicking.
Bioorthogonal reactions are widely used to study important processes in cells, and these applications have had a huge impact on the fields of biology and biochemistry. Researchers can detect how biomolecules interact within cells and can image them without interfering with living cells. In disease research, bioorthogonal reactions can be used not only to study patients’ cells, but also to study pathogens: proteins in bacteria can be labeled to track their movements in the body. The researchers also began developing engineered antibodies that can click on their tumor targets to provide anti-cancer treatments more accurately.
"These very important achievements and these very wonderful discoveries of our three winners have really had a huge impact on chemistry and science as a whole," Ramstrom said. "For this reason, this is indeed the greatest benefit to mankind."
Who is the winner of the Nobel Prize in Chemistry in recent years?
Last year, Benjamin List and David MacMillan won awards for developing asymmetric organic catalysis. In 2020, Emmanuelle Charpentier and Jennifer Doudna were recognized for their development of CRISPR/Cas9 gene editing.John Goodenough, M. Stanley Whittingham and Akira Yoshino shared the 2019 Lithium Ion Battery Development Award, “The Hidden Force in the Mobile Age.” The 2018 award was awarded to Frances H. Arnold, George P. Smith and Gregory P. Winter for leveraging the power of evolution to produce new beneficial enzymes for pharmaceuticals, renewable energy, industrial chemistry and many other fields. In 2017, Jacques Dubochet, Joachim Frank and Richard Henderson shared awards for improving bioimaging status.
