Congratulations to Carolyn R. Bertozzi (Stanford University), Morten Meldal (University of Copenhagen) and K. Barry Sharpless (Scripps Institute) - winners of the 2022 Nobel Prize in chemistry. These renowned scientists were awarded the honor for their development of click chemistry and bioorthogonal chemistry. Sharpless now joins a select group of five scientists who are two-time Nobel laureates (he received his first Nobel Prize in 2001 for his work on chiral oxidation catalysis).

What is Click Chemistry?

The term “click chemistry” was coined by Sharpless in the late 1990s, and is a reference to the modular nature of the process. At a high level, click chemistry uses simple and practical reactions to join molecular entities, which can then be adapted to a variety of different applications. (The “click” refers to the satisfying sound that a luggage strap makes when it is snapped together, or when one building block is attached to another. Even if the two components are inherently different, their ability to click together signifies a connection, enabling them to form a partnership of sorts.)

Working independently, Sharpless and Meldal demonstrated what was to become the preeminent molecular combination in click chemistry: azides and alkyne (the compatibility of which was first discovered by German chemist Rolf Huisgen in the 1960s). These two “click partners” bond exceptionally well together in the presence of a copper catalyst, enabling high-yielding, reliable and accessible reactions without undesirable byproducts.

Bioorthogonal Chemistry: Expanding Click Chemistry’s Reach

Unfortunately, the toxicity of copper ions rendered this particular click chemistry reaction unusable within living cells. To solve the issue, Bertozzi built upon the foundations of click chemistry and took them a step further by removing the copper catalyst and “clicking” the molecules together in a different formation. The result: bioorthogonal chemistry, a term Bertozzi created to describe the use of click chemistry inside biological cells.

Click Chemistry in Drug Development

While click chemistry is scalable to many different methods of use, the relative ease with which it can be adapted to living organisms offers particular advantages from a drug development standpoint. It’s quick, versatile and safe, and drug synthesis using click chemistry doesn’t require extensive purification. Click chemistry has the capability to be more targeted than traditional methods of drug testing; when developing medications to treat certain cancers, for example, click chemistry has enabled researchers to pinpoint specific cells without disturbing others.

Click chemistry has evolved steadily in the 25 years since its emergence, and will likely continue to grow in influence as scientists adapt new ways to incorporate it into their work. By awarding the Nobel Prize to those who have done the most to develop and expand this exciting technique, the scientific community recognizes the enormous potential of click chemistry in cell biology, drug development and much more.

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