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The 2022 Nobel Prize in Chemistry for the development of click chemistry and bioorthogonal chemistry

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Abstract

The 2022 Nobel Prize in Chemistry recognized the development of biorthogonal chemical ligation reactions known as click chemistry in biomedicine. This concept has catalyzed significant progress in sensing and diagnosis, chemical biology, materials chemistry, and drug discovery and delivery. In proteomics, the ability to incorporate a click tag into proteins has propelled development of powerful new methods for selective enrichment of protein complexes that inform understanding of protein networks. It also has had a strong influence on the ability to enrich for protein post-translational modifications. This feature article summarizes the impacts of biorthogonal click chemistry on proteomics.

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References

  1. Kolb HC, Finn MG, Sharpless KB. Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed Engl. 2001;40(11):2004–21.

    Article  CAS  Google Scholar 

  2. Tornøe CW, Christensen C, Meldal M. Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J Org Chem. 2002;67(9):3057–64.

    Article  Google Scholar 

  3. Dong R, Yang X, Wang B, Ji X. Mutual leveraging of proximity effects and click chemistry in chemical biology. Medicinal Research Reviews.n/a(n/a):1–24.

  4. Schreiber CL, Smith BD. Molecular conjugation using non-covalent click chemistry. Nat Rev Chem. 2019;3(6):393–400.

    Article  CAS  Google Scholar 

  5. Wu D, Yang K, Zhang Z, Feng Y, Rao L, Chen X, et al. Metal-free bioorthogonal click chemistry in cancer theranostics. Chem Soc Rev. 2022;51(4): 1336–76.

  6. Mahal LK, Yarema KJ, Bertozzi CR. Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis. Science. 1997;276(5315):1125–8.

    Article  CAS  Google Scholar 

  7. Saxon E, Bertozzi CR. Cell surface engineering by a modified staudinger reaction. Science. 2000;287(5460):2007–10.

    Article  CAS  Google Scholar 

  8. Prescher JA, Dube DH, Bertozzi CR. Chemical remodelling of cell surfaces in living animals. Nature. 2004;430(7002):873–7.

    Article  CAS  Google Scholar 

  9. Agard NJ, Prescher JA, Bertozzi CR. A strain-promoted [3 + 2] azide−alkyne cycloaddition for covalent modification of biomolecules in living systems. J Am Chem Soc. 2004;126(46):15046–7.

    Article  CAS  Google Scholar 

  10. Laughlin ST, Baskin JM, Amacher SL, Bertozzi CR. In vivo imaging of membrane-associated glycans in developing zebrafish. Science. 2008;320(5876):664–7.

    Article  CAS  Google Scholar 

  11. Parker CG, Pratt MR. Click chemistry in proteomic investigations. Cell. 2020;180(4):605–32.

    Article  CAS  Google Scholar 

  12. Smith LM, Kelleher NL. Proteoform: a single term describing protein complexity. Nat Methods. 2013;10(3):186–7.

    Article  CAS  Google Scholar 

  13. Aebersold R, Agar JN, Amster IJ, Baker MS, Bertozzi CR, Boja ES, et al. How many human proteoforms are there? Nat Chem Biol. 2018;14(3):206–14.

    Article  CAS  Google Scholar 

  14. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. P Natl Acad Sci USA. 2005;102(43):15545–50.

    Article  CAS  Google Scholar 

  15. Hogrebe A, von Stechow L, Bekker-Jensen DB, Weinert BT, Kelstrup CD, Olsen JV. Benchmarking common quantification strategies for large-scale phosphoproteomics. Nat Commun. 2018;9(1):1045.

    Article  Google Scholar 

  16. Ho Y, Gruhler A, Heilbut A, Bader GD, Moore L, Adams SL, et al. Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature. 2002;415(6868):180–3.

    Article  CAS  Google Scholar 

  17. Adelmant G, Garg BK, Tavares M, Card JD, Marto JA. Tandem affinity purification and mass spectrometry (TAP-MS) for the analysis of protein complexes. Curr Protoc Protein Sci. 2019;96(1): e84.

    Article  Google Scholar 

  18. Cho KF, Branon TC, Udeshi ND, Myers SA, Carr SA, Ting AY. Proximity labeling in mammalian cells with TurboID and split-TurboID. Nat Protoc. 2020;15(12):3971–99.

    Article  CAS  Google Scholar 

  19. Weerapana E, Wang C, Simon GM, Richter F, Khare S, Dillon MB, et al. Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature. 2010;468(7325):790–5.

    Article  CAS  Google Scholar 

  20. Zhao Q, Ouyang X, Wan X, Gajiwala KS, Kath JC, Jones LH, et al. Broad-spectrum kinase profiling in live cells with lysine-targeted sulfonyl fluoride probes. J Am Chem Soc. 2017;139(2):680–5.

    Article  CAS  Google Scholar 

  21. Lapinsky DJ, Johnson DS. Recent developments and applications of clickable photoprobes in medicinal chemistry and chemical biology. Future Med Chem. 2015;7(16):2143–71.

    Article  CAS  Google Scholar 

  22. Hart GW, Ball LE. Post-translational modifications: a major focus for the future of proteomics. Mol Cell Proteomics. 2013;12(12):3443.

    Article  CAS  Google Scholar 

  23. Dennis JW. Genetic code asymmetry supports diversity through experimentation with posttranslational modifications. Curr Opin Chem Biol. 2017;41:1–11.

    Article  CAS  Google Scholar 

  24. Zachara NE, Akimoto Y, Boyce M, Hart GW. The O-GlcNAc modification. In: Varki A, Cummings RD, Esko JD, Stanley P, Hart GW, Aebi M, et al., editors. Essentials of Glycobiology. 4th ed. Cold Spring Harbor (NY)2022. p. 251–64.

  25. Ma J, Wang WH, Li Z, Shabanowitz J, Hunt DF, Hart GW. O-GlcNAc site mapping by using a combination of chemoenzymatic labeling, copper-free click chemistry, reductive cleavage, and electron-transfer dissociation mass spectrometry. Anal Chem. 2019;91(4):2620–5.

    Article  CAS  Google Scholar 

  26. Hinneburg H, Stavenhagen K, Schweiger-Hufnagel U, Pengelley S, Jabs W, Seeberger PH, et al. The art of destruction: optimizing collision energies in quadrupole-time of flight (Q-TOF) instruments for glycopeptide-based glycoproteomics. J Am Soc Mass Spectrom. 2016;27(3):507–19.

    Article  CAS  Google Scholar 

  27. Woo CM, Iavarone AT, Spiciarich DR, Palaniappan KK, Bertozzi CR. Isotope-targeted glycoproteomics (IsoTaG): a mass-independent platform for intact N- and O-glycopeptide discovery and analysis. Nat Methods. 2015;12(6):561–7.

    Article  CAS  Google Scholar 

  28. Charron G, Zhang MM, Yount JS, Wilson J, Raghavan AS, Shamir E, et al. Robust fluorescent detection of protein fatty-acylation with chemical reporters. J Am Chem Soc. 2009;131(13):4967–75.

    Article  CAS  Google Scholar 

  29. Kulkarni RA, Worth AJ, Zengeya TT, Shrimp JH, Garlick JM, Roberts AM, et al. Discovering targets of non-enzymatic acylation by thioester reactivity profiling. Cell Chem Biol. 2017;24(2):231–42.

    Article  CAS  Google Scholar 

  30. Islam K, Chen Y, Wu H, Bothwell IR, Blum GJ, Zeng H, et al. Defining efficient enzyme-cofactor pairs for bioorthogonal profiling of protein methylation. P Natl Acad Sci USA. 2013;110(42):16778–83.

    Article  CAS  Google Scholar 

  31. Kalesh K, Lukauskas S, Borg AJ, Snijders AP, Ayyappan V, Leung AKL, et al. An integrated chemical proteomics approach for quantitative profiling of intracellular ADP-ribosylation. Sci Rep. 2019;9(1):6655.

    Article  Google Scholar 

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Funding

The author is supported by the US National Institute for General Medical Sciences grant R35GM144090.

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  1. Dept. of Biochemistry, Boston University, 670 Albany St. Rm. 509, Boston, MA, 02118, USA

    Joseph Zaia

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  1. Joseph Zaia
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Zaia, J. The 2022 Nobel Prize in Chemistry for the development of click chemistry and bioorthogonal chemistry. Anal Bioanal Chem 415, 527–532 (2023). https://doi.org/10.1007/s00216-022-04483-9

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