How is Click Chemistry Used in Drug Discovery?

Of all the sectors revolutionised by click chemistry, drug discovery is one of the most significant. In an article published in the peer-reviewed journal Expert Opinion on Drug Discovery, the authors explore how click chemistry is used to accelerate critical steps like lead discovery and optimisation.

They mention copper-catalyzed azide-alkyne cycloaddition (CuAAC), the game-changing ‘click reaction’ introduced by chemists Morten Meldal and Barry Sharpless in the early 2000s. It empowered scientists with a simple, reliable and user-friendly way to connect building blocks using covalent chemical bonds.

“Click chemistry reactions are an important part of the medicinal chemistry toolbox and offer substantial advantages to medicinal chemists in terms of overcoming the limitations of useful chemical synthesis, increasing throughput, and improving the quality of compound libraries,” reads the abstract.

The role of bioorthogonal reactions

Meldal and Sharpless went on to receive the Nobel Prize in Chemistry 2022 for their work on click reactions. American chemist Carolyn Bertozzi was also recognised for her work on bioorthogonal reactions. By eliminating the copper catalyst, Bertozzi made click reactions suitable for use within living organisms. Bioorthogonal reactions don’t disrupt normal cell chemistry, which makes them ideal for tracking natural biological processes. This opened exciting new avenues for drug discovery.

Click chemistry and cancer research

In the UK, researchers used click chemistry to develop a novel method to study proteins. Working from the Francis Crick Institute and Imperial College London, the team used a technique called bioorthogonal cell line-specific tagging of glycoproteins (BOCTAG) to identify proteins and track their source of cellular origin. The findings were published in the journal Nature Communications and explain how BOCTAG could help scientists understand more about cancer and other diseases.

Click chemistry and SARS-CoV-2

Click chemistry has also played an important role in the fight against SARS-CoV-2. With new variants an ongoing risk, scientists are attempting to develop antiviral medications that can be easily tweaked when new mutations emerge. Click chemistry is being used to modify small interfering RNAs (siRNAs) in antiviral medications designed to fight SARS-CoV-2.

In an article published in the journal Angewandte Chemie, the team explain how siRNA medications can be optimised to protect cells against new SARS-CoV-2 variants. The results are impressive, with the team maintaining these adjustments can slash viral loads and cytotoxicity.

“The adjustment of the siRNA sequence allows a rapid adaptation of their antiviral activity against different variants of concern,” reads the article. “The ability to conjugate the siRNA via click-chemistry to receptor ligands facilitates the construction of targeted siRNAs for a flexible antiviral defence strategy.”

Want to know more about the different applications for click chemistry? We cover all bases in our complete guide, ‘What is Click Chemistry? Everything You Need to Know’.