Click Chemistry and Bioorthogonal Reactions: Why They Get Nobel Prizes

The Nobel Prize in Chemistry in 2022 was awarded to Carolyn Bertozzi, Morten Meldal and Barry Sharpless. Scientists have been developing click chemistry and bioorthogonal reactions. Understanding the value of their discoveries

What happened

  • On October 5, the Royal Swedish Academy of Sciences announced the names of the 2022 Nobel Prize winners in Chemistry. They became Caroline R. Bertocci (USA), Morten Meldal (Denmark), C. Barry Sharpless (USA). Scientists received an award for their contribution to the development of click chemistry and bioorthogonal chemistry.
  • An American scientist is considered the founder of click chemistry. Barry Sharpless. In 2001, he proposed using a new approach in chemistry that would allow the synthesis of organic molecules on an industrial scale. The scientist was sure that it was time for chemists to stop imitating natural processes, since it takes a lot of time, and during the synthesis a large amount of unnecessary impurities are formed that are difficult to remove. This approach hinders the development of new pharmaceuticals.
  • To solve the problem, Sharpless proposed click chemistry, a direction that develops the creation of universal tools for building complex molecular systems. The essence of the method lies in the fact that during the synthesis, not the carbon skeletons of molecules are connected, as in nature, but the molecules of oxygen and nitrogen added to them, serving as a kind of molecular fasteners (hence the “click” in the name). Such a molecular constructor is assembled more efficiently and at the same time produces a minimum of impurities that are easy to remove.
  • Morten Meldal and Barry Sharpless simultaneously presented to the scientific community in 2002 a chemical reaction called “Cu(I)-catalyzed azide-alkyne cycloaddition”. In it, the atoms of azide and alkyd groups acted as two parts of the “fastener”, and copper became the catalyst. This reaction can take place at a temperature close to room temperature.
  • Biochemist Caroline Bertocci managed to develop click reactions that do not violate the normal chemistry of the cell – she called them bioorthogonal. Thanks to her discovery, scientists can now attach markers to molecules for biochemical research without the danger of damaging the cell.

What does it mean

Sharpless became the founder of click chemistry, and Meldala and Bertozzi brought it to a new level. Currently, scientists from various fields rely on their developments. For example, without click chemistry it is now impossible to imagine the development of drugs, DNA modification, the synthesis of nanoparticles and polymers.

And Carolyn Bertozzip’s bioorthogonal reactions helped advance the development of pharmaceutical drugs for cancer. She used bioorthogonal reactions to study the glycans (complex carbohydrates in cell membranes) produced by tumors. The results of her research led to the creation of a drug that breaks down glycans that are harmful to the body.

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