Click Chemistry: The Nobel Prize Winner Being Used in the Penn State Department of Chemistry
It was announced in early October that the developers and forerunning utilizers of click chemistry and bioorthogonal chemistry were awarded the 2022 Nobel Prize in Chemistry. Winners Carolyn Bertozzi, Morten Meldal, and Barry Sharpless have all contributed to laying the foundation of click chemistry and improving its functionalism. Some of its uses are included in the development of pharmaceuticals, potential cancer treatments, various biological applications, and mapping DNA.
What is click chemistry?
Click chemistry is considered a kind of framework for doing chemistry. It is a process whereby new molecules can be formed quickly and reliably based on the way two chemical moieties react. It provides a robust strategy for linking small organic molecules to nanoparticle surfaces. Chemists can independently make a nanoparticle and a molecule for its surface, and then "click" them together for the desired application. These groups of reactions are modular, much quicker and simple to use, easy to purify, and versatile. Click chemistry can be applied in many different research areas including pharmaceutical sciences, polymer chemistry, and materials sciences.
The application of click chemistry is prolific around Penn State’s Department of Chemistry. Many of our researchers in different research areas make use of click chemistry daily; others have developed budding interests in pursuing the use of click chemistry in future research. Read below how our faculty and students have been impacted by click chemistry and why its discovery and recognition by the Nobel Prize is so important:
“Our group’s research lies at the interface of organic synthesis and polymer chemistry, and the use of click chemistry has had a profound influence on both areas. We can utilize click chemistry to install desirable functionalities (e.g., catalysts) onto designer monomers or polymer backbones with the specificity and fidelity of natural systems. By stapling these units together, we can build up complexity of our target molecules and macromolecules in an atom economical way. The pioneering works of Bertozzi, Meldel, and Sharpless are indeed responsible for beginning to ‘click' fields like ours together, cultivating much interdisciplinary work since inception. Awarding the Nobel Prize to these scientists for their contributions is also recognizing the impact this discovery continues to have by enabling nascent interdisciplinary research areas to develop." - Beth Elacqua, Assistant Professor of Chemistry
"In the Showalter Lab, we study intrinsically disordered proteins and put "molecular probes" such as spin labels or fluorophores in them to measure their interactions with themselves or with binding partners. Incorporating probes in traditional ways through cysteine chemistry could be problematic because native cysteines must be mutated to prevent non-specific labeling. But such mutation can alter the intrinsic properties of proteins. Click chemistry is a powerful tool that, when combined with unnatural amino acids, enables placing the probe anywhere in a protein with precision and ease, and allows us to study intrinsically disordered proteins in a more native context." - Wei Chen, post-doctoral student in the Showalter Lab
“My field of research is RNA chemistry, and it has been no exception to the impact of click chemistry; for example, we use reagents that react with accessible parts of the RNA and then separate those from the unreacted ones by “clicking” a handle onto the reacted RNA molecules and pulling that part of the RNA out with a magnet. This increases the sensitivity of the experiment many times over. Biochemists like us can do chemistry in a single step in a complex mixture, and that is why this invention was awarded the Nobel Prize.” - Phil Bevilacqua, Department Head of Chemistry
"Click chemistry opened the door to modifications (labeling) of proteins without needing extensive amino acid substitutions. Following many successful examples, my group is interested in installing “clickable” unnatural amino acids at specific sites on the surface of proteins, and then “click” paramagnetic labels to those sites by using spectroscopy to measure the distance between them. With this approach, we can access a wealth of information about the dynamics of proteins and structures of hard-to-study oligomeric systems such as amyloid fibrils." - Alexey Silakov, Assistant Professor of Chemistry
“While my lab doesn’t use click chemistry, the discovery of click chemistry has had an impact in our general field of inorganic and materials research. Nanoparticles that are used in many applications, including medical diagnostics and therapeutics, have organic molecules on their surfaces. These organic molecules can be designed to enhance the functions of nanoparticles. This allows them to be biocompatible, to target certain types of cells, and to deliver drugs, among many other functions.” - Ray Schaak, DuPont Professor of Materials Chemistry
The diverse use of Click Chemistry is illustrated by these examples in our own department. It is because the technique is so general and powerful that it won the Nobel Prize in Chemistry!