This year's Nobel Prize in Chemistry was won by the American Carolyn R. Bertozzi, Morten Meldal from Denmark and the American chemist K. Barry Sharpless for the development of click chemistry and bioorthogonal chemistry. The discovery has a remarkably broad scope and has advanced both organic chemistry and medical biology. Its outcomes have been incorporated into almost every area of the life sciences.
“The essence of click chemistry is that it is capable of quickly and selectively connecting molecules. Without producing byproducts, it is able to mimic the simplicity of reactions playing out in nature to create connections,” explains chemist Zoltán Kónya, deputy rector at the University of Szeged. He added that this allows the progress of diseases to be examined on the cellular level whereby even the movement of a single molecule can be followed by means of dye or isotope markers, for instance.
“Chemists researching drugs are always working towards creating larger molecules with increasingly complex properties but comprising smaller, simpler elements. Until now, however, the synthesis of such large molecules has been very expensive and time-consuming. This is why researchers have sought reactions that make it possible to quickly and effectively make connections, even in a particular order, between the constituent components in a water-based environment at room temperature,” says Péter Kele, senior scientific research fellow at the ELKH Research Centre for Natural Sciences (TTK) and someone who also conducts research in this area, by way of explanation for the discovery. Sharpless provided a summary of the reactions suitable for these transformations in a notice dating back to 2000, in which he coined the phrase ‘click reactions’. Not much later, Sharpless, and simultaneously, but independently, Meldal, recorded the copper ion catalyzed azide–alkyne cycloaddition reaction, which has since become the best known click reaction.
It is thanks to the work of Bertozzi that it has become possible to make click reactions biocompatible through bioorthogonal chemistry, which can be applied to living systems. These biocompatible, selective reactions provided the foundations for a new area of science known as chemical biology. According to the researcher, the biological systems – proteins, nucleic acids and carbohydrates – to be examined in the course of chemical biology processes can be transformed by synthetically manufactured small molecules, even without disrupting the functioning of the living cells. This makes it possible to map the biochemical processes taking place within living organisms.
Péter Kele added that several such biocompatible click reactions have been identified in recent years, and that bioothogonal chemistry is now no longer only applicable to the connection of molecules, but also to the release of active ingredients in pharmaceuticals, for example. This makes it possible to selectively release an active ingredient in the vicinity of cancer cells, for instance.
“Click chemistry is increasingly indispensible in biological research and diagnostics,” emphasized Péter Kele. The researcher and the Chemical Biology Research Group he leads at TTK are working on the development of inexpensive and effective fluorescent markers that can in future be used for imaging procedures, biological testing, the monitoring of biochemical processes and the early diagnosis of cancer. In addition, they are also researching how the combination of bioorthogonal chemistry and light can be used to selectively release active ingredients. For example, the process would make it possible to provide light-controlled chemotherapy, which would reduce the side-effects of the treatment.