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EDITORIALS & ARTICLES
Discuss the basics of click and bioorthogonal chemistry and its applications
The 2022 Nobel Prize in Chemistry has been awarded to chemists Carolyn R. Bertozzi and K. Barry Sharpless from the U.S., and Morten Meldal from Denmark, for their work in the field of click chemistry and bioorthogonal chemistry.
Dr. Sharpless was the first scientist to work on what is today called click chemistry – a branch of science that explores the assembly of molecules. In fact, this is not his first Nobel Prize in Chemistry. He previously won the award in 2001.
Click chemistry involves reactions that unite two synthetic molecules quickly and irreversibly. Some of these reactions can be carried out inside living cells without disrupting biochemical processes, making them “bioorthogonal.”
This approach is used to tag biomolecules with fluorescent probes that illuminate the inner workings of cellular biochemistry, for example, and it also offers a way to produce antibody-drug conjugates that have highly targeted therapeutic action in the body. Click chemistry is even being directly applied inside patients, in ongoing clinical trials of a powerful cancer therapy.
The need for click chemistry
Replicating reactions that involve bonds between carbon atoms – that are vital to the existence of life – is expensive and often leads to side reactions and loss of material. Instead of trying to make carbon atoms react with each other, These molecules can further be linked using oxygen or nitrogen atoms as bridges. Simpler reactions, “where there is a strong intrinsic drive for the molecules to bond together”, may avoid the loss of material as well as the unwanted side reactions.
Click chemistry has applications in drug development and delivery, DNA sequencing, and functional materials as well as studying biologic processes, which allows a better understanding of disease and therapeutics to treat them.
“A technique like this could be very important in terms of thinking about personalized medicine” as this chemistry allows scientists to target specific cells and specific molecules within cells.
When synthesizing molecules — bringing two molecules together to create one larger molecule — there is always the chance for side reactions, where the molecules don’t react in the desired way and create unwanted side products instead. This is especially true in biological contexts, where there are many metabolites and other biomolecules floating around.