Nobel Prize in Chemistry 2022
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Nobel Prize in Chemistry 2022

Author: ChemistryViews

The Nobel Prize in Chemistry 2022 has been awarded to

  • Carolyn R. Bertozzi, Stanford University, CA, USA,
  • Morten Meldal, University of Copenhagen, Denmark, and
  • K. Barry Sharpless, Scripps Research, La Jolla, CA, USA,

for “the development of click chemistry and bioorthogonal chemistry” [1].

 

Research

Barry Sharpless and Morten Meldal have laid the foundation for click chemistry—reactions in which molecular building blocks snap together quickly and efficiently. Carolyn Bertozzi has taken click chemistry to a new level and started using it in living organisms.

 

Barry Sharpless and Morten Meldal

Barry Sharpless, who is awarded his second Nobel Prize in Chemistry, developed the concept of click chemistry [2], which is a form of simple and reliable chemistry where reactions occur quickly and unwanted by-products are avoided. He argues that researchers could link simple molecules together using bridges of nitrogen or oxygen atoms. Combining simple chemical building blocks makes it possible to create an almost endless variety of molecules, which is particularly useful in drug development.

Shortly afterward, Morten Meldal and Barry Sharpless—independently of each other—presented what is now the perfect example of click chemistry: the copper-catalyzed azide-alkyne cycloaddition, giving triazoles. This is an elegant and efficient chemical reaction that is in widespread use. Among many other uses, it is used in the development of pharmaceuticals, for mapping DNA, and for creating functional materials.

Meldal discovered this reaction while trying to react an alkyne with an acyl halide in the presence of copper ions. He found that the alkyne had reacted with an azide group that was present in the acyl halide reaction partner, forming a triazole. He first presented his discovery at a symposium in 2001 and published an article in 2002 [3].

The same year, Sharpless published a paper about the copper-catalyzed azide-alkyne cycloaddition [4], showing that the reaction works in water and is reliable. He described it as an “ideal” click reaction. Sharpless proposed that chemists can use the reaction to easily link different molecules, which turned out to be right. If chemists want to link two different molecules they can now, relatively easily, introduce an azide in one molecule and an alkyne in the other. They then “snap” the molecules together with the help of some copper ions.

 

Carolyn Bertozzi

Carolyn Bertozzi took click chemistry to a new level. To map glycanes on the surface of cells, she developed click reactions that work inside living organisms. Mapping glycans had been challenging due to a lack of efficient tools. Bertozzi wondered whether she could get cells to produce a sialic acid—one of the sugars that build up glycans—with a chemical handle, making the glycans easier to map. She could, for example, then attach a fluorescent molecule to the handle.

In 2000, Bertozzi found the optimal chemical handle: an azide [5]. She modified a Staudinger reaction and used it to connect a fluorescent molecule to the azide she had introduced to the cells’ glycans. Because the azide does not affect the cells, it can be introduced into living organisms.

With azides as a chemical handle on cells, the copper-catalyzed azide-alkyne cycloaddition was also interesting for the functionalization of biomolecules—but copper is toxic. Thus, Bertozzi developed a copper-free click reaction, called the strain-promoted alkyne-azide cycloaddition [6]. This is based on the observation that azides and alkynes can react without the help of copper if the alkyne is forced into a ring-shaped chemical structure.

Bertozzi’s bioorthogonal reactions take place without disrupting the normal chemistry of the cell. These reactions are widely used to explore cells and track biological processes. Using bioorthogonal reactions, researchers have, e.g., improved the targeting of anticancer drugs that are now being tested in clinical trials.

 

Laureates

Carolyn Bertozzi, born in 1966 in the USA, studied chemistry at Harvard University, Cambridge, MA, USA, and at the University of California (UC) Berkeley, USA, where she received her Ph.D. in 1993. After postdoctoral work at UC San Francisco, USA, in the field of cellular immunology, she joined the faculty of UC Berkeley in 1996. In 2015, Carolyn Bertozzi joined Stanford University. Today, she serves as Anne T. and Robert M. Bass Professor of Chemistry and Professor of Chemical & Systems Biology and Radiology there, as well as an Investigator at the Howard Hughes Medical Institute.

Among many other honors, Carolyn Bertozzi has received the Ernst Schering Prize from the Schering Foundation in 2007, the Lemelson-MIT Prize from the Lemelson Foundation and the Massachusetts Institute of Technology (MIT) in 2010, the Heinrich Wieland Prize from the Boehringer Ingelheim Foundation in 2012, and the Arthur C. Cope Award from the American Chemical Society (ACS) in 2017. She is a Fellow of the U.S. National Academy of Inventors and of the American Association for the Advancement of Science (AAAS), as well as a Member of the U.S. National Academy of Sciences, the American Academy of Arts and Sciences, and the German Academy of Sciences Leopoldina.

 

Morten P. Meldal, born on January 16, 1954, in Denmark, studied chemical engineering at the Technical University of Denmark (DTU), Lyngby, where he received his Ph.D. in 1983 on the synthesis of oligosaccharides. As a post-doctoral fellow, he was at the University of Cambridge, UK, at the MRC Laboratory of Molecular Biology. In 1996, he became a professor at the Technical University of Denmark. He also headed the Solid Phase Organic Combinatorial Chemistry Center at the Carlsberg Laboratory, Copenhagen, Denmark, with the rank of professor from 1988. In 2004, he received an honorary professorship in the Department of Pharmacy at the University of Copenhagen. In 2011, he became Professor of Nanochemistry at the University of Copenhagen’s Nano Science Center.

Among several other awards, Morten Meldal received the Ralph F. Hirschmann Award in Peptide Chemistry in 2009 and the Vincent du Vigneaud Award in 2011. He is a member of the Royal Danish Academy of Sciences.

 

K. Barry Sharpless, born on April 28, 1941, in Philadelphia, PA, USA, studied chemistry at Dartmouth College, Hanover, NH, USA, and Stanford University, CA, USA, where he received his Ph.D. in organic chemistry in 1968. He then performed postdoctoral research with James P. Collman at Stanford and with Konrad E. Bloch at Harvard University, Cambridge, MA, USA. In 1970, Barry Sharpless joined the Massachusetts Institute of Technology (MIT), Cambridge. From 1977 to 1980, he was part of the faculty at Stanford University. Since 1990, he is W. M. Keck Professor at the Scripps Research Institute.

Among many other honors, Barry Sharpless has received the Nobel Prize in Chemistry in 2001, together with William Standish Knowles and Ryōji Noyori, “for his work on chirally catalyzed oxidation reactions”, the 2019 Priestley Medal of the American Chemical Society (ACS), and the 2015 August Wilhelm von Hofmann Lecture of the German Chemical Society (GDCh).

 

References

[1] NobelPrize.org

[2] Hartmuth C. Kolb, M. G. Finn, K. Barry Sharpless, Click Chemistry: Diverse Chemical Function from a Few Good Reactions, Angew. Chem. Int. Ed. 2001, 40, 2004–2021. https://doi.org/10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5

[3] Christian W. Tornøe, Caspar Christensen, Morten Meldal, Peptidotriazoles on Solid Phase: [1,2,3]-Triazoles by Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides, J. Org. Chem. 2002, 67, 3057–3064. https://doi.org/10.1021/jo011148j

[4] Vsevolod V. Rostovtsev, Luke G. Green, Valery V. Fokin, K. Barry Sharpless, A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal Alkynes, Angew. Chem. Int. Ed. 2002, 41, 2596–2599. https://doi.org/10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4

[5] Eliana Saxon, Carolyn R. Bertozzi, Cell Surface Engineering by a Modified Staudinger Reaction, Science 2000, 287, 2007–2010. https://doi.org/10.1126/science.287.5460.2007

[6] Nicholas J. Agard, Jennifer A. Prescher, Carolyn R. Bertozzi, A Strain-Promoted [3 + 2] Azide−Alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems, J. Am. Chem. Soc. 2004, 126, 15046–15047. https://doi.org/10.1021/ja044996f

Selected Publications by Carolyn R. Bertozzi


Selected Publications by Morten P. Meldal


Selected Publications by K. Barry Sharpless

 

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