The term bioorthogonal chemistry refers to any chemical reaction that can occur inside of living systems without interfering with native biochemical processes.[1][2][3] The term was coined by Carolyn R. Bertozzi in 2003.[4][5] Since its introduction, the concept of the bioorthogonal reaction has enabled the study of biomolecules such as glycans, proteins,[6] and lipids[7] in real time in living systems without cellular toxicity. A number of chemical ligation strategies have been developed that fulfill the requirements of bioorthogonality, including the 1,3-dipolar cycloaddition between azides and cyclooctynes (also termed copper-free click chemistry),[8] between nitrones and cyclooctynes,[9] oxime/hydrazone formation from aldehydes and ketones,[10] the tetrazine ligation,[11] the isocyanide-based click reaction,[12] and most recently, the quadricyclane ligation.[13]
Shown here is a bioorthogonal ligation between biomolecule X and reactive partner Y. To be considered bioorthogonal, these reactive partners cannot perturb other chemical functionality naturally found within the cell.
The use of bioorthogonal chemistry typically proceeds in two steps. First, a cellular substrate is modified with a bioorthogonal functional group (chemical reporter) and introduced to the cell; substrates include metabolites, enzyme inhibitors, etc. The chemical reporter must not alter the structure of the substrate dramatically to avoid affecting its bioactivity. Secondly, a probe containing the complementary functional group is introduced to react and label the substrate.
Although effective bioorthogonal reactions such as copper-free click chemistry have been developed, development of new reactions continues to generate orthogonal methods for labeling to allow multiple methods of labeling to be used in the same biosystems. Carolyn R. Bertozzi was awarded the Nobel Prize in Chemistry in 2022 for her development of click chemistry and bioorthogonal chemistry.[14]
^Sletten, Ellen M.; Bertozzi, Carolyn R. (2009). "Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality". Angewandte Chemie International Edition. 48 (38): 6974–98. doi:10.1002/anie.200900942. PMC 2864149. PMID 19714693.
^Prescher, Jennifer A.; Dube, Danielle H.; Bertozzi, Carolyn R. (2004). "Chemical remodelling of cell surfaces in living animals". Nature. 430 (7002): 873–7. Bibcode:2004Natur.430..873P. doi:10.1038/nature02791. PMID 15318217. S2CID 4371934.
^Prescher, Jennifer A; Bertozzi, Carolyn R (2005). "Chemistry in living systems". Nature Chemical Biology. 1 (1): 13–21. doi:10.1038/nchembio0605-13. PMID 16407987. S2CID 40548615.
^Hang, Howard C.; Yu, Chong; Kato, Darryl L.; Bertozzi, Carolyn R. (2003-12-09). "A metabolic labeling approach toward proteomic analysis of mucin-type O-linked glycosylation". Proceedings of the National Academy of Sciences. 100 (25): 14846–14851. Bibcode:2003PNAS..10014846H. doi:10.1073/pnas.2335201100. ISSN 0027-8424. PMC 299823. PMID 14657396.
^Sletten, Ellen M.; Bertozzi, Carolyn R. (2011). "From Mechanism to Mouse: A Tale of Two Bioorthogonal Reactions". Accounts of Chemical Research. 44 (9): 666–676. doi:10.1021/ar200148z. PMC 3184615. PMID 21838330.
^Plass, Tilman; Milles, Sigrid; Koehler, Christine; Schultz, Carsten; Lemke, Edward A. (2011). "Genetically Encoded Copper-Free Click Chemistry". Angewandte Chemie International Edition. 50 (17): 3878–3881. doi:10.1002/anie.201008178. PMC 3210829. PMID 21433234.
^Neef, Anne B.; Schultz, Carsten (2009). "Selective Fluorescence Labeling of Lipids in Living Cells". Angewandte Chemie International Edition. 48 (8): 1498–500. doi:10.1002/anie.200805507. PMID 19145623.
^Baskin, J. M.; Prescher, J. A.; Laughlin, S. T.; Agard, N. J.; Chang, P. V.; Miller, I. A.; Lo, A.; Codelli, J. A.; Bertozzi, C. R. (2007). "Copper-free click chemistry for dynamic in vivo imaging". Proceedings of the National Academy of Sciences. 104 (43): 16793–7. Bibcode:2007PNAS..10416793B. doi:10.1073/pnas.0707090104. PMC 2040404. PMID 17942682.
^Yarema, K. J.; Mahal, LK; Bruehl, RE; Rodriguez, EC; Bertozzi, CR (1998). "Metabolic Delivery of Ketone Groups to Sialic Acid Residues. Application to Cell Surface Glycoform Engineering". Journal of Biological Chemistry. 273 (47): 31168–79. doi:10.1074/jbc.273.47.31168. PMID 9813021.
^Blackman, Melissa L.; Royzen, Maksim; Fox, Joseph M. (2008). "The Tetrazine Ligation: Fast Bioconjugation based on Inverse-electron-demand Diels-Alder Reactivity". Journal of the American Chemical Society. 130 (41): 13518–9. doi:10.1021/ja8053805. PMC 2653060. PMID 18798613.
^Stöckmann, Henning; Neves, André A.; Stairs, Shaun; Brindle, Kevin M.; Leeper, Finian J. (2011). "Exploring isonitrile-based click chemistry for ligation with biomolecules". Organic & Biomolecular Chemistry. 9 (21): 7303–5. doi:10.1039/C1OB06424J. PMID 21915395.
^Sletten, Ellen M.; Bertozzi, Carolyn R. (2011). "A Bioorthogonal Quadricyclane Ligation". Journal of the American Chemical Society. 133 (44): 17570–3. doi:10.1021/ja2072934. PMC 3206493. PMID 21962173.
^"The Nobel Prize in Chemistry". The Nobel Prize. Retrieved 6 October 2022.
and 28 Related for: Bioorthogonal chemistry information
The term bioorthogonalchemistry refers to any chemical reaction that can occur inside of living systems without interfering with native biochemical processes...
deprotection of functional groups independently of each other. The term bioorthogonalchemistry refers to any chemical reaction that can occur inside of living...
Sharpless, "for the development of click chemistry and bioorthogonalchemistry". Click chemistry is a method for attaching a probe or substrate of interest...
developmental processes and anomalies. Recent advancements in bioorthogonalchemistry have revealed applications in protein analysis. The extension of...
for her wide-ranging work spanning both chemistry and biology. She coined the term "bioorthogonalchemistry" for chemical reactions compatible with living...
Quantum chemistry, also called molecular quantum mechanics, is a branch of physical chemistry focused on the application of quantum mechanics to chemical...
Chemistry (Swedish: Nobelpriset i kemi) is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry...
fungicides and plant retardants. However, triazoles are also useful in bioorthogonalchemistry, because the large number of nitrogen atoms causes triazoles to...
or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry...
Bertozzi and Morten P. Meldal, "for the development of click chemistry and bioorthogonalchemistry". Sharpless is the fifth person (in addition to two organizations)...
syndicated comic strip Bicyclononyne, a small molecule used in the bioorthogonalchemistry of antibody-drug conjugates Board Certified in Neurofeedback, a...
JS (1981). "The Anatomy and Taxonomy of Proteins". Advances in Protein Chemistry. 34: 167–339. doi:10.1016/S0065-3233(08)60520-3. PMID 7020376. Archived...
Boston, Massachusetts, U.S. "for the development of click chemistry and bioorthogonalchemistry" 2022 K. Barry Sharpless Philadelphia, Pennsylvania, U.S...
Morten Meldal who won the prize in chemistry in 2022 for the development of click chemistry and bioorthogonalchemistry. To date, of the 14 Nobel Prizes...
findings. Bioorthogonalchemistry The term was coined by Carolyn Bertozzi in 2003. Since its introduction, the concept of the bioorthogonal reaction has...
Da Silva JJ, Williams RJ (1991). The Biological Chemistry of the Elements: The Inorganic Chemistry of Life. Clarendon Press. ISBN 0-19-855598-9. Nicholls...
Engelbrecht; Euan Ward; Oliver Whang (October 5, 2022). "Nobel Prize in Chemistry Is Awarded to 3 Scientists for Work 'Snapping Molecules Together'". The...
California, Berkeley to work on bioorthogonalchemistry. In particular, Sletten made use of bioorthogonalchemistry for the labelling of living systems...
of basic or applied chemistry. 2022 - Carolyn R. Bertozzi - for Bioorthogonalchemistry 2020 – Emmanuelle Charpentier and Jennifer Doudna – for CRISPR...
"The 2022 chemistry Nobel prize goes to bioorthogonal and click chemistry – as it happened". Chemistry World. Royal Society of Chemistry. Retrieved 26...
and inorganic chemistry. All types of chemistry are required, with emphasis on biochemistry, organic chemistry and physical chemistry. Basic classes...
diffraction, by Theodore Svedberg who received the 1962 Nobel Prize in Chemistry. The first tertiary protein structure, that of myoglobin, was published...
fermentation of sucrose "zymase". In 1907, he received the Nobel Prize in Chemistry for "his discovery of cell-free fermentation". Following Buchner's example...
terpenoids. Phytochemistry can be considered a subfield of botany or chemistry. Activities can be led in botanical gardens or in the wild with the aid...
Prescher and Carolyn R. Bertozzi, the developers of bioorthogonalchemistry, defined bioorthogonal chemical reporters as "non-native, non-perturbing chemical...
Global Information