Then, in 2003,\u00a0Carolyn Bertozzi<\/a>\u00a0proposed that click chemistry could be used in studies of biological systems to make it easier to observe vital cellular processes without interfering with them. Bertozzi called this \u201cbioorthogonal\u201d chemistry in\u00a0a paper<\/a>\u00a0she and her colleagues published that year. The term has since been\u00a0widely-adopted term<\/a>\u00a0in the field.<\/p>\n The ability to perform complex reactions in living systems without interfering with natural biological reactions made it possible to study molecules and cellular processes in cells and\u00a0inside complex organisms<\/a>\u00a0such as zebra fish, rather than in laboratory dishes. It has already helped scientists understand an important protein processing reaction called glycosylation, helped to develop molecular imaging molecules that could detect disease in living organisms, and opened up the possibility of selectively delivering drugs to\u00a0particular tissues in the body<\/a>.<\/p>\n These findings have \u201cled to a revolution in how chemists think about linking molecules together and how to do it in living cells,\u201d \u00c5qvist said.<\/p>\n Today\u2019s announcement marks the second time that Sharpless has won a Nobel Prize in Chemistry.\u00a0In 2001<\/a>, he shared the prize with William Knowles and Ryoji Noyori for the development of catalytic asymmetric synthesis.<\/p>\n What is click chemistry?<\/strong><\/p>\n Sharpless spent much of the 1990s considering the need to find less cumbersome ways to synthesize complex molecules. His thinking culminated in\u00a0a 2001 paper<\/a>\u00a0in which he and his co-authors proposed the term \u201cclick chemistry\u201d to refer to any reaction that links together molecular building blocks in an efficient, specific and quick manner. Shortly after the publication of the paper, Meldal and Sharpless independently discovered the first click chemistry reaction: a highly useful one called the copper-catalyzed azide-alkyne cycloaddition.<\/p>\n On one side of the reaction is an azide, a molecule that has three nitrogen atoms in a row. On the other side is an alkyne, a molecule in which two carbon atoms are bonded together with a triplet bond. By themselves, these two building blocks aren\u2019t very reactive: Mixed together, they are slow to react and yield a mixture of products. But Meldal and Sharpless separately realized that if they added a bit of copper to the mix, the reaction accelerated dramatically and led primarily to a stable product known as a triazole.<\/p>\n By strategically adding azide and alkyne \u201ctags\u201d to molecules, chemists can use this copper-catalyzed reaction to link them precisely into much larger molecules with specific structures.<\/p>\n The copper-catalyzed reaction immediately gained \u201cenormous interest\u201d across chemistry and related fields, said Olof Ramstr\u00f6m of the Nobel committee during the announcement. Although other click chemistry reactions have been found, \u201cthis particular reaction has almost become synonymous with the click chemistry concept and is also often called the click reaction,\u201d Ramstr\u00f6m said. \u201cYou can say that it\u2019s still the crown jewel of click reactions.\u201d<\/p>\n What is bioorthogonal chemistry?<\/strong><\/p>\n In 2003, Bertozzi coined the term \u201cbioorthogonal chemistry\u201d for any kind of chemical reaction that could occur within a living system without interfering with it or harming it. It\u2019s click chemistry that can be applied to living organisms.<\/p>\n The seeds for this idea sprouted in the 1990s, when Bertozzi began studying a particular\u00a0glycan<\/a>, or complex sugar found on the surface of cells. Conducting research on this glycan wasn\u2019t easy with the chemical techniques available to her at the time. But after hearing another scientist give a seminar on coaxing cells to produce an unnatural sugar molecule, Bertozzi was inspired to consider whether she could do something similar to\u00a0map the glycans on cells<\/a>. That\u2019s when her work on bioorthogonal chemistry began.<\/p>\n How is bioorthogonal chemistry used to study living systems?<\/strong><\/p>\n Bertozzi came up with a simple way to track glycans on a cell. First, she grew cells near a modified sugar that was linked to an azide. The cells up took up the modified sugar and incorporated it into glycans on their surface. Then Bertozzi added to the mixture an alkyne that had a fluorescent molecule attached to it. The alkyne underwent a click reaction with the modified sugar and attached the fluorescent molecule to it. With that simple reaction, the glycans glowed green, and that allowed Bertozzi to track their movements across cell membranes under a microscope.<\/p>\n Today, Bertozzi, a professor at Stanford University, tracks glycans found on the surface of tumor cells. This work enabled her to discover that certain glycans protect tumor cells from the body\u2019s immune system. Her findings have opened up avenues for cancer immune therapy, with many researchers working to find \u201cclickable\u201d antibodies to target different types of tumors. Bertozzi and her team are also working on this problem. They have created a new drug, currently in clinical trials, that targets and destroys glycans on the surface of tumor cells.<\/p>\n What are other applications for click chemistry and bioorthogonal chemistry?<\/strong><\/p>\n Tracking the movements of molecules through and across cells is just one of many applications for click chemistry and bioorthogonal chemistry.<\/p>\n A major advantage of the techniques is that they don\u2019t introduce unwanted byproducts into reaction mixtures \u2014 they function with a clean efficiency that allows scientists to carefully craft complex molecules for a variety of purposes.<\/p>\n Click chemistry has enabled massive strides in\u00a0drug development<\/a>,\u00a0DNA sequencing<\/a>, the\u00a0synthesis of \u201csmart\u201d materials<\/a>\u00a0and almost any other application in which chemists need to simply connect pairs of building blocks, Ramstr\u00f6m said. Researchers can now easily add functionality to a wide range of materials, for example by clicking in chemical extensions that can conduct electricity or capture sunlight.<\/p>\n Bioorthogonal reactions are used widely to investigate vital processes in cells, and those applications have had an enormous impact on the fields of biology and biochemistry. Researchers can probe how biomolecules interact within cells, and they can image living cells without disturbing them. In studies of disease, bioorthogonal reactions are useful for studying not just the cells of patients but also those of pathogens: The proteins in bacteria can be labeled to follow their movements through the body. Researchers are also starting to develop engineered antibodies that can click onto their tumor targets to deliver cancer-killing therapeutics more precisely.<\/p>\n \u201cThese very important accomplishments and these really fantastic discoveries from our three laureates have really made an enormous impact on chemistry and on science in general,\u201d Ramstr\u00f6m said. \u201cFor that, it\u2019s really been to the greatest benefit of humankind.\u201d<\/p>\n Who won the Nobel Prize in Chemistry in recent years?<\/strong><\/p>\n Last year, Benjamin List and David MacMillan won the prize for their\u00a0development of asymmetrical organocatalysis<\/a>. In 2020, Emmanuelle Charpentier and\u00a0Jennifer Doudna<\/a>\u00a0were recognized for their\u00a0development of CRISPR\/Cas9 genetic editing<\/a>. John Goodenough, M. Stanley Whittingham and Akira Yoshino shared the 2019 prize for\u00a0developing lithium-ion batteries<\/a>, \u201cthe hidden workhorses of the mobile era.\u201d The 2018 prize went to Frances H. Arnold, George P. Smith and Gregory P. Winter for\u00a0harnessing the power of evolution<\/a>\u00a0to produce novel, beneficial enzymes used in pharmaceuticals, renewable energy, industrial chemistry and many other fields. And in 2017, Jacques Dubochet, Joachim Frank and Richard Henderson shared the prize for\u00a0improving the state of biological imaging<\/a>.<\/p>\n![\"\"](\"https:\/\/www.fie.undef.edu.ar\/ceptm\/wp-content\/uploads\/2022\/10\/chemistry_graphic-REVISED_chem_click_desktop.jpg\")
![\"\"](\"https:\/\/www.fie.undef.edu.ar\/ceptm\/wp-content\/uploads\/2022\/10\/Nobel-Timeline-chemistry3_chemistry_desktop-scaled.jpg\")
![\"\"](\"https:\/\/www.fie.undef.edu.ar\/ceptm\/wp-content\/uploads\/2022\/10\/chemistry_graphic-REVISED_chem_cells_desktop.jpg\")