The 2022 Nobel Prize in Chemistry has been awarded to Carolyn R. Bertozzi, Morten Meldal and K. Barry Sharpless “for the development of click chemistry and bioorthogonal chemistry”.
Sharpless and Meldal have laid the foundation for a functional form of chemistry – click chemistry – in which molecular building blocks snap together quickly and efficiently. Bertozzi has taken click chemistry to a new dimension and started utilizing it in living organisms.
This is the 2nd Nobel prize for K. Barry Sharpless; Sharpless was awarded half of the 2001 Nobel Prize in Chemistry "for his work on chirally catalysed oxidation reactions".
About the Nobel Laureates
Carolyn R. Bertozzi
Professor at Stanford University
Born: 1966, Boston
PhD 1993 from UC Berkeley
Morten Meldal
Professor at University of Copenhagen, Denmark
Born 1954, Denmark
PhD 1983 from Technical University of Denmark
K. Barry Sharpless
Professor at Scripps Research, La Jolla, CA, USA
Born 1941, Philadelphia
PhD 1968, Stanford University
Reactions from the Nobel Laureates
Post-announcement Interviews
Click Chemistry
In click chemistry, new complex molecules are synthesized using simpler molecular building blocks that snap together quickly and efficiently.
Instead of trying to wrangle reluctant carbon atoms into reacting with each other, Barry Sharpless discovered the idea to start with smaller molecules that already had a complete carbon frame. These simple molecules could then be linked together using bridges of nitrogen atoms or oxygen atoms, which are easier to control. If chemists choose simple reactions – where there is a strong intrinsic drive for the molecules to bond together – they avoid many of the side reactions, with a minimal loss of material.
From www.quantamagazine.org/… -
Meldal and Sharpless independently discovered the first click-chemistry reaction: a highly useful one called the copper-catalyzed azide-alkyne cycloaddition.
On one side of the reaction is an azide, a molecule that has three nitrogen atoms in a row. On the other side of the reaction is an alkyne, a molecule in which two carbon atoms are bonded together with a triplet bond. By themselves, these two building blocks aren’t very reactive: Mixed together, they are slow to react and yield a mixture of products. But Meldal and Sharpless separately realized that if they added a bit of copper to the mix, the reaction accelerated dramatically and led primarily to a stable product known as a triazole.
By strategically adding azide and alkyne “tags” to molecules, chemists can use this copper-catalyzed reaction to link them precisely into much larger molecules with specific structures.
A summary by Sharpless and others -
Lecture on Click Chemistry by K. Barry Sharpless
Bioorthogonal Chemistry
In 2003, Bertozzi coined the term “bioorthogonal chemistry” for any kind of chemical reaction that could occur within a living system without interfering or harming it. It’s click chemistry that can be applied to living organisms. Copper was a no-no.
The seeds for this idea sprouted in the 1990s, when Bertozzi began to study a particular glycan, or complex sugar found on the surface of cells.
In 2004, she published the copper-free click reaction, called the strain-promoted alkyne-azide cycloaddition – and then demonstrated that it can be used to track glycans.
From www.nobelprize.org/...
One area that Bertozzi focuses on is glycans on the surface of tumour cells. Her studies have led to the insight that some glycans appear to protect tumours from the body’s immune system, as they make the immune cells shut down. To block this protective mechanism, Bertozzi and her colleagues have created a new type of biological pharmaceutical. They have joined a glycan-specific antibody to enzymes that break down the glycans on the surface of the tumour cells. This pharmaceutical is now being tested in clinical trials on people with advanced cancer.
Many researchers have also started to develop clickable antibodies that target a range of tumours. Once the antibodies attach to the tumour, a second molecule that clicks to the antibody is injected. For example, this could be a radioisotope that can be used to track tumours using a PET scanner or that can aim a lethal dose of radiation at the cancer cells.
Small documentary on Carolyn Bertozzi and her research -
TED Talk by Carolyn Bertozzi
Applications of these Technologies
Click chemistry is utilized in the development of pharmaceuticals, for mapping DNA and creating materials that are more fit for purpose. Using bioorthogonal reactions, researchers have improved the targeting of cancer pharmaceuticals.
From www.quantamagazine.org/… -
The ability to perform complex reactions in living systems without interfering with natural biological reactions made it possible to study diseases inside cells or even inside complex organisms such as zebrafish rather than in laboratory dishes. It has already helped scientists understand an important protein processing reaction called glycosylation, helped to develop molecular imaging molecules that could detect disease in living organisms and opened up the possibility of selectively delivering drugs to particular tissues in the body.
Additional Coverage
Congratulations
Nobel Prize Awards Schedule
- PHYSIOLOGY OR MEDICINE – Monday, 3 October (awarded)
- PHYSICS – Tuesday, 4 October (awarded)
- CHEMISTRY – Wednesday, 5 October (awarded)
- LITERATURE – Thursday, 6 October
- PEACE – Friday, 7 October
- THE SVERIGES RIKSBANK PRIZE IN ECONOMIC SCIENCES IN MEMORY OF ALFRED NOBEL – Monday, 10 October
Epilogue
Congratulations to these pioneers and may the future be driven by science and logic, not politics.
Let’s hear from those of you here who have a deeper understanding of this field and additional insights into the life and career of these luminaries.
Further Reading
- www.nobelprize.org
- Press release: www.nobelprize.org/...
- Popular information: www.nobelprize.org/...
- Advanced information: www.nobelprize.org/...
- The 2022 Nobel Prize in Physiology or Medicine awarded to Svante Pääbo, pioneer in Palaeogenetics — www.dailykos.com/…
- The 2022 Nobel Prize in Physics awarded for the science of Quantum Entanglement — www.dailykos.com/...