Topics in Current Chemistry

, 374:2 | Cite as

Transition-Metal-Catalyzed Bioorthogonal Cycloaddition Reactions

  • Maiyun Yang
  • Yi Yang
  • Peng R. Chen
Part of the following topical collections:
  1. Cycloadditions in Bioorthogonal Chemistry


In recent years, bioorthogonal reactions have emerged as a powerful toolbox for specific labeling and visualization of biomolecules, even within the highly complex and fragile living systems. Among them, copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction is one of the most widely studied and used biocompatible reactions. The cytotoxicity of Cu(I) ions has been greatly reduced due to the use of Cu(I) ligands, which enabled the CuAAC reaction to proceed on the cell surface, as well as within an intracellular environment. Meanwhile, other transition metals such as ruthenium, rhodium and silver are now under development as alternative sources for catalyzing bioorthogonal cycloadditions. In this review, we summarize the development of CuAAC reaction as a prominent bioorthogonal reaction, discuss various ligands used in reducing Cu(I) toxicity while promoting the reaction rate, and illustrate some of its important biological applications. The development of additional transition metals in catalyzing cycloaddition reactions will also be briefly introduced.


Bioorthogonal reaction Transition metal Cycloaddition reaction CuAAC reaction Unnatural amino acids 


  1. 1.
    Wang Q, Chan TR, Hilgraf R, Fokin VV, Sharpless KB, Finn MG (2003) Bioconjugation by copper(I)-catalyzed azide–alkyne [3 + 2] cycloaddition. J Am Chem Soc 125:3192–3193CrossRefGoogle Scholar
  2. 2.
    Fokin VV (2007) Click imaging of biochemical processes in living systems. ACS Chem Biol 2:775–778CrossRefGoogle Scholar
  3. 3.
    Kolb HC, Sharpless KB (2003) The growing impact of click chemistry on drug discovery. Drug Discov Today 8:1128–1137CrossRefGoogle Scholar
  4. 4.
    Zheng T, Rouhanifard SH, Jalloh AS, Wu P (2012) Click triazoles for bioconjugation. Top Heterocycl Chem 28:163–183Google Scholar
  5. 5.
    Gupta SS, Kuzelka J, Singh P, Lewis WG, Manchester M, Finn MG (2005) Accelerated bioorthogonal conjugation: a practical method for the ligation of diverse functional molecules to a polyvalent virus scaffold. Bioconjug Chem 16:1572–1579CrossRefGoogle Scholar
  6. 6.
    Song W, Wang Y, Yu Z, Vera CIR, Qu J, Lin Q (2010) A metabolic alkene reporter for spatiotemporally controlled imaging of newly synthesized proteins in mammalian cells. ACS Chem Biol 5:875–885CrossRefGoogle Scholar
  7. 7.
    Wang J, Zhang W, Song W, Wang Y, Yu Z, Li J, Wu M, Wang L, Zang J, Lin Q (2010) A biosynthetic route to photoclick chemistry on proteins. J Am Chem Soc 132:14812–14818CrossRefGoogle Scholar
  8. 8.
    Agard NJ, Prescher JA, Bertozzi CR (2004) A strain-promoted [3 + 2] azide–alkyne cycloaddition for covalent modification of biomolecules in living systems. J Am Chem Soc 126:15046–15047CrossRefGoogle Scholar
  9. 9.
    Blackman ML, Royzen M, Fox JM (2008) Tetrazine ligation: fast bioconjugation based on inverse-electron-demand Diels–Alder reactivity. J Am Chem Soc 130:13518–13519CrossRefGoogle Scholar
  10. 10.
    Devaraj NK, Weissleder R, Hilderbrand SA (2008) Tetrazine-based cycloadditions: application to pretargeted live cell imaging. Bioconjug Chem 19:2297–2299CrossRefGoogle Scholar
  11. 11.
    Prescher JA, Bertozzi CR (2005) Chemistry in living systems. Nat Chem Biol 1:13–21CrossRefGoogle Scholar
  12. 12.
    Lim RKV, Lin Q (2010) Bioorthogonal chemistry: recent progress and future directions. Chem Commun 46:1589–1600CrossRefGoogle Scholar
  13. 13.
    Grammel M, Hang HC (2013) Chemical reporters for biological discovery. Nat Chem Biol 9:475–484CrossRefGoogle Scholar
  14. 14.
    Beatty KE, Fisk JD, Smart BP, Lu YY, Szychowski J, Hangauer MJ, Baskin JM, Bertozzi CR, Tirrell DA (2010) Live-cell imaging of cellular proteins by a strain-promoted azide–alkyne cycloaddition. Chembiochem 11:2092–2095CrossRefGoogle Scholar
  15. 15.
    Lewis WG, Green LG, Grynszpan F, Radić Z, Carlier PR, Taylor P, Finn MG, Sharpless KB (2002) Click chemistry in situ: acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks. Angew Chem Int Ed 41:1053–1057CrossRefGoogle Scholar
  16. 16.
    Lewis WG, Magallon FG, Fokin VV, Finn MG (2004) Discovery and characterization of catalysts for azide–alkyne cycloaddition by fluorescence quenching. J Am Chem Soc 126:9152–9153CrossRefGoogle Scholar
  17. 17.
    Presolski SI, Hong V, Cho S-H, Finn MG (2010) Tailored ligand acceleration of the cu-catalyzed azide–alkyne cycloaddition reaction: practical and mechanistic implications. J Am Chem Soc 132:14570–14576CrossRefGoogle Scholar
  18. 18.
    Uttamapinant C, Tangpeerachaikul A, Grecian S, Clarke S, Singh U, Slade P, Gee KR, Ting AY (2012) Fast, cell-compatible click chemistry with copper-chelating azides for biomolecular labeling. Angew Chem Int Ed 51:5852–5856CrossRefGoogle Scholar
  19. 19.
    Codelli JA, Baskin JM, Agard NJ, Bertozzi CR (2008) Second-generation difluorinated cyclooctynes for copper-free click chemistry. J Am Chem Soc 130:11486–11493CrossRefGoogle Scholar
  20. 20.
    Ning X, Guo J, Wolfert MA, Boons G-J (2008) Visualizing metabolically labeled glycoconjugates of living cells by copper-free and fast huisgen cycloadditions. Angew Chem Int Ed 47:2253–2255CrossRefGoogle Scholar
  21. 21.
    Baskin JM, Bertozzi CR (2007) Bioorthogonal click chemistry: covalent labeling in living systems. QSAR Comb Sci 26:1211–1219CrossRefGoogle Scholar
  22. 22.
    Plass T, Milles S, Koehler C, Schultz C, Lemke EA (2011) Genetically encoded copper-free click chemistry. Angew Chem Int Ed 50:3878–3881CrossRefGoogle Scholar
  23. 23.
    Lang K, Davis L, Torres-Kolbus J, Chou C, Deiters A, Chin JW (2012) Genetically encoded norbornene directs site-specific cellular protein labelling via a rapid bioorthogonal reaction. Nat Chem 4:298–304CrossRefGoogle Scholar
  24. 24.
    Plass T, Milles S, Koehler C, Szymański J, Mueller R, Wießler M, Schultz C, Lemke EA (2012) Amino acids for Diels–Alder reactions in living cells. Angew Chem Int Ed 51:4166–4170CrossRefGoogle Scholar
  25. 25.
    Song W, Wang Y, Qu J, Lin Q (2008) Selective functionalization of a genetically encoded alkene-containing protein via “photoclick chemistry” in bacterial cells. J Am Chem Soc 130:9654–9655CrossRefGoogle Scholar
  26. 26.
    Song W, Wang Y, Qu J, Madden MM, Lin Q (2008) A photoinducible 1,3-dipolar cycloaddition reaction for rapid, selective modification of tetrazole-containing proteins. Angew Chem Int Ed 47:2832–2835CrossRefGoogle Scholar
  27. 27.
    Yu Z, Pan Y, Wang Z, Wang J, Lin Q (2012) Genetically encoded cyclopropene directs rapid, photoclick-chemistry-mediated protein labeling in mammalian cells. Angew Chem Int Ed 51:10600–10604CrossRefGoogle Scholar
  28. 28.
    An P, Yu Z, Lin Q (2013) Design of oligothiophene-based tetrazoles for laser-triggered photoclick chemistry in living cells. Chem Commun 49:9920–9922CrossRefGoogle Scholar
  29. 29.
    Best MD (2009) Click chemistry and bioorthogonal reactions: unprecedented selectivity in the labeling of biological molecules. Biochemistry 48:6571–6584CrossRefGoogle Scholar
  30. 30.
    El-Sagheer AH, Brown T (2010) Click chemistry with DNA. Chem Soc Rev 39:1388–1405CrossRefGoogle Scholar
  31. 31.
    Yang M, Li J, Chen PR (2014) Transition metal-mediated bioorthogonal protein chemistry in living cells. Chem Soc Rev 43:6511–6526CrossRefGoogle Scholar
  32. 32.
    Hein JE, Fokin VV (2010) Copper-catalyzed azide–alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(I) acetylides. Chem Soc Rev 39:1302–1315CrossRefGoogle Scholar
  33. 33.
    Huisgen R (1963) 1,3-Dipolar cycloadditions. past and future. Angew Chem Int Ed 2:565–598CrossRefGoogle Scholar
  34. 34.
    Rostovtsev VV, Green LG, Fokin VV, Sharpless KB (2002) A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed 41:2596–2599CrossRefGoogle Scholar
  35. 35.
    Tornøe CW, Christensen C, Meldal M (2002) Peptidotriazoles on solid phase: [1 − 3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J Org Chem 67:3057–3064CrossRefGoogle Scholar
  36. 36.
    Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed 40:2004–2021CrossRefGoogle Scholar
  37. 37.
    Pasini D (2013) The click reaction as an efficient tool for the construction of macrocyclic structures. Molecules 18:9512–9530CrossRefGoogle Scholar
  38. 38.
    Liang L, Astruc D (2011) The copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) “click” reaction and its applications. An overview. Coord Chem Rev 255:2933–2945CrossRefGoogle Scholar
  39. 39.
    Hein C, Liu X-M, Wang D (2008) Click chemistry, a powerful tool for pharmaceutical sciences. Pharm Res 25:2216–2230CrossRefGoogle Scholar
  40. 40.
    Himo F, Lovell T, Hilgraf R, Rostovtsev VV, Noodleman L, Sharpless KB, Fokin VV (2005) Copper(I)-catalyzed synthesis of azoles. DFT study predicts unprecedented reactivity and intermediates. J Am Chem Soc 127:210–216CrossRefGoogle Scholar
  41. 41.
    Worrell BT, Malik JA, Fokin VV (2013) Direct evidence of a dinuclear copper intermediate in Cu(I)-catalyzed azide–alkyne cycloadditions. Science 340:457–460CrossRefGoogle Scholar
  42. 42.
    Meldal M, Tornøe CW (2008) Cu-catalyzed azide–alkyne cycloaddition. Chem Rev 108:2952–3015CrossRefGoogle Scholar
  43. 43.
    Chan TR, Hilgraf R, Sharpless KB, Fokin VV (2004) Polytriazoles as copper(I)-stabilizing ligands in catalysis. Org Lett 6:2853–2855CrossRefGoogle Scholar
  44. 44.
    Rodionov VO, Presolski SI, Díaz Díaz D, Fokin VV, Finn MG (2007) Ligand-accelerated Cu-catalyzed azide–alkyne cycloaddition: a mechanistic report. J Am Chem Soc 129:12705–12712CrossRefGoogle Scholar
  45. 45.
    Schoffelen S, Lambermon MHL, Eldijk MBV, Hest JCMV (2008) Site-specific modification of Candida antarctica lipase B via residue-specific incorporation of a non-canonical amino acid. Bioconjug Chem 19:1127–1131CrossRefGoogle Scholar
  46. 46.
    Link AJ, Tirrell DA (2003) Cell surface labeling of escherichia coli via copper(I)-Catalyzed [3 + 2] cycloaddition. J Am Chem Soc 125:11164–11165CrossRefGoogle Scholar
  47. 47.
    Hong V, Steinmetz NF, Manchester M, Finn MG (2010) Labeling live cells by copper-catalyzed alkyne–azide click chemistry. Bioconjug Chem 21:1912–1916CrossRefGoogle Scholar
  48. 48.
    Besanceney-Webler C, Jiang H, Zheng T, Feng L, Soriano del Amo D, Wang W, Klivansky LM, Florence L, Liu Y, Wu P (2011) Increasing the efficacy of bioorthogonal click reactions for bioconjugation: a comparative study. Angew Chem Int Ed 50:8051–8056CrossRefGoogle Scholar
  49. 49.
    Yang M, Song Y, Zhang M, Lin S, Hao Z, Liang Y, Zhang D, Chen PR (2012) Converting a solvatochromic fluorophore into a protein-based pH indicator for extreme acidity. Angew Chem Int Ed 51:7674–7679CrossRefGoogle Scholar
  50. 50.
    Wang W, Hong S, Tran A, Jiang H, Triano R, Liu Y, Chen X, Wu P (2011) Sulfated ligands for the copper(I)-catalyzed azide–alkyne cycloaddition. Chem Asian J 6:2796–2802CrossRefGoogle Scholar
  51. 51.
    Yang M, Jalloh AS, Wei W, Zhao J, Wu P, Chen PR (2014) Biocompatible click chemistry enabled compartment-specific pH measurement inside E. coli. Nat Commun 5:4981CrossRefGoogle Scholar
  52. 52.
    Soriano del Amo D, Wang W, Jiang H, Besanceney C, Yan AC, Levy M, Liu Y, Marlow FL, Wu P (2010) Biocompatible copper(I) catalysts for in vivo imaging of glycans. J Am Chem Soc 132:16893–16899CrossRefGoogle Scholar
  53. 53.
    Kennedy DC, McKay CS, Legault MCB, Danielson DC, Blake JA, Pegoraro AF, Stolow A, Mester Z, Pezacki JP (2011) Cellular consequences of copper complexes used to catalyze bioorthogonal click reactions. J Am Chem Soc 133:17993–18001CrossRefGoogle Scholar
  54. 54.
    Link AJ, Vink MKS, Tirrell DA (2004) Presentation and detection of azide functionality in bacterial cell surface proteins. J Am Chem Soc 126:10598–10602CrossRefGoogle Scholar
  55. 55.
    Hong V, Presolski SI, Ma C, Finn MG (2009) Analysis and optimization of copper-catalyzed azide–alkyne cycloaddition for bioconjugation. Angew Chem Int Ed 48:9879–9883CrossRefGoogle Scholar
  56. 56.
    Brotherton WS, Michaels HA, Simmons JT, Clark RJ, Dalal NS, Zhu L (2009) Apparent copper(II)-accelerated azide–alkyne cycloaddition. Org Lett 11:4954–4957CrossRefGoogle Scholar
  57. 57.
    Kuang G-C, Michaels HA, Simmons JT, Clark RJ, Zhu L (2010) Chelation-assisted, copper(II)-acetate-accelerated azide–alkyne cycloaddition. J Org Chem 75:6540–6548CrossRefGoogle Scholar
  58. 58.
    Jiang H, Zheng T, Lopez-Aguilar A, Feng L, Kopp F, Marlow FL, Wu P (2014) Monitoring dynamic glycosylation in vivo using super-sensitive click chemistry. Bioconjug Chem 25:698–706CrossRefGoogle Scholar
  59. 59.
    Sletten EM, Bertozzi CR (2009) Bioorthogonal chemistry: fishing for selectivity in a sea of functionality. Angew Chem Int Ed 48:6974–6998CrossRefGoogle Scholar
  60. 60.
    Patterson DM, Nazarova LA, Prescher JA (2014) Finding the right (bioorthogonal) chemistry. ACS Chem Biol 9:592–605CrossRefGoogle Scholar
  61. 61.
    Zheng M, Zheng L, Zhang P, Li J, Zhang Y (2015) Development of bioorthogonal reactions and their applications in bioconjugation. Molecules 20:3190CrossRefGoogle Scholar
  62. 62.
    Thirumurugan P, Matosiuk D, Jozwiak K (2013) Click chemistry for drug development and diverse chemical-biology applications. Chem Rev 113:4905–4979CrossRefGoogle Scholar
  63. 63.
    Peng T, Yuan X, Hang HC (2014) Turning the spotlight on protein–lipid interactions in cells. Curr Opin Chem Biol 21:144–153CrossRefGoogle Scholar
  64. 64.
    Martell J, Weerapana E (2014) Applications of copper-catalyzed click chemistry in activity-based protein profiling. Molecules 19:1378–1393CrossRefGoogle Scholar
  65. 65.
    El-Sagheer AH, Brown T (2012) Click nucleic acid ligation: applications in biology and nanotechnology. Acc Chem Res 45:1258–1267CrossRefGoogle Scholar
  66. 66.
    Nischan N, Hackenberger CPR (2014) Site-specific PEGylation of proteins: recent developments. J Org Chem 79:10727–10733CrossRefGoogle Scholar
  67. 67.
    Jing C, Cornish VW (2011) Chemical tags for labeling proteins inside living cells. Acc Chem Res 44:784–792CrossRefGoogle Scholar
  68. 68.
    Lang K, Chin JW (2014) Bioorthogonal reactions for labeling proteins. ACS Chem Biol 9:16–20CrossRefGoogle Scholar
  69. 69.
    Johnson JA, Lu YY, Van Deventer JA, Tirrell DA (2010) Residue-specific incorporation of non-canonical amino acids into proteins: recent developments and applications. Curr Opin Chem Biol 14:774–780CrossRefGoogle Scholar
  70. 70.
    Liu CC, Schultz PG (2010) Adding new chemistries to the genetic code. Annu Rev Biochem 79:413–444CrossRefGoogle Scholar
  71. 71.
    Hinner MJ, Johnsson K (2010) How to obtain labeled proteins and what to do with them. Curr Opin Biotechnol 21:766–776CrossRefGoogle Scholar
  72. 72.
    Uttamapinant C, White KA, Baruah H, Thompson S, Fernández-Suárez M, Puthenveetil S, Ting AY (2010) A fluorophore ligase for site-specific protein labeling inside living cells. Proc Natl Acad Sci USA 107:10914–10919CrossRefGoogle Scholar
  73. 73.
    Chin JW (2014) Expanding and reprogramming the genetic code of cells and animals. Annu Rev Biochem 83:379–408CrossRefGoogle Scholar
  74. 74.
    Wang Q, Parrish AR, Wang L (2009) Expanding the genetic code for biological studies. Chem Biol 16:323–336CrossRefGoogle Scholar
  75. 75.
    Tyagi S, Lemke EA (2013) Chapter 9—genetically encoded click chemistry for single-molecule FRET of proteins. In: Conn Pm (ed) vol 113, Academic Press, pp 169–187Google Scholar
  76. 76.
    Lin S, Yan H, Li L, Yang M, Peng B, Chen S, Li W, Chen PR (2013) Site-specific engineering of chemical functionalities on the surface of live hepatitis D virus. Angew Chem Int Ed 52:13970–13974CrossRefGoogle Scholar
  77. 77.
    Beatty KE, Xie F, Wang Q, Tirrell DA (2005) Selective dye-labeling of newly synthesized proteins in bacterial cells. J Am Chem Soc 127:14150–14151CrossRefGoogle Scholar
  78. 78.
    Beatty KE, Liu JC, Xie F, Dieterich DC, Schuman EM, Wang Q, Tirrell DA (2006) Fluorescence visualization of newly synthesized proteins in mammalian cells. Angew Chem Int Ed 118:7524–7527CrossRefGoogle Scholar
  79. 79.
    Kang H, Schuman EM (1996) A requirement for local protein synthesis in neurotrophin-induced hippocampal synaptic plasticity. Science 273:1402–1406CrossRefGoogle Scholar
  80. 80.
    Martin KC, Casadio A, Zhu H, Yaping E, Rose JC, Chen M, Bailey CH, Kandel ER (1997) Synapse-specific, long-term facilitation of aplysia sensory to motor synapses: a function for local protein synthesis in memory storage. Cell 91:927–938CrossRefGoogle Scholar
  81. 81.
    Dieterich DC, Hodas JJL, Gouzer G, Shadrin IY, Ngo JT, Triller A, Tirrell DA, Schuman EM (2010) In situ visualization and dynamics of newly synthesized proteins in rat hippocampal neurons. Nat Neurosci 13:897–905CrossRefGoogle Scholar
  82. 82.
    Lewin GR, Barde Y-A (1996) Physiology of the Neurotrophins. Annu Rev Neurosci 19:289–317CrossRefGoogle Scholar
  83. 83.
    Schwarz F, Aebi M (2011) Mechanisms and principles of N-linked protein glycosylation. Curr Opin Struct Biol 21:576–582CrossRefGoogle Scholar
  84. 84.
    Hang HC, Bertozzi CR (2005) The chemistry and biology of mucin-type O-linked glycosylation. Bioorg Med Chem 13:5021–5034CrossRefGoogle Scholar
  85. 85.
    Chen X, Varki A (2010) Advances in the biology and chemistry of sialic acids. ACS Chem Biol 5:163–176CrossRefGoogle Scholar
  86. 86.
    Dube DH, Bertozzi CR (2003) Metabolic oligosaccharide engineering as a tool for glycobiology. Curr Opin Chem Biol 7:616–625CrossRefGoogle Scholar
  87. 87.
    Jiang H, English BP, Hazan RB, Wu P, Ovryn B (2015) Tracking surface glycans on live cancer cells with single-molecule sensitivity. Angew Chem Int Ed 54:1765–1769CrossRefGoogle Scholar
  88. 88.
    Dube DH, Bertozzi CR (2005) Glycans in cancer and inflammation [mdash] potential for therapeutics and diagnostics. Nat Rev Drug Discov 4:477–488CrossRefGoogle Scholar
  89. 89.
    Kannagi R, Izawa M, Koike T, Miyazaki K, Kimura N (2004) Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis. Cancer Sci 95:377–384CrossRefGoogle Scholar
  90. 90.
    Liu Y-C, Yen H-Y, Chen C-Y, Chen C-H, Cheng P-F, Juan Y-H, Chen C-H, Khoo K-H, Yu C-J, Yang P-C, Hsu T-L, Wong C-H (2011) Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells. Proc Natl Acad Sci USA 108:11332–11337CrossRefGoogle Scholar
  91. 91.
    Du J, Hong S, Dong L, Cheng B, Lin L, Zhao B, Chen Y-G, Chen X (2015) Dynamic sialylation in transforming growth factor-β (TGF-β)-induced epithelial to mesenchymal transition. J Biol Chem 290:12000–12013CrossRefGoogle Scholar
  92. 92.
    Woo CM, Iavarone AT, Spiciarich DR, Palaniappan KK, Bertozzi CR (2015) Isotope-targeted glycoproteomics (IsoTaG): a mass-independent platform for intact N- and O-glycopeptide discovery and analysis. Nat Meth 12:561–567CrossRefGoogle Scholar
  93. 93.
    van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9:112–124CrossRefGoogle Scholar
  94. 94.
    Resh MD (2006) Trafficking and signaling by fatty-acylated and prenylated proteins. Nat Chem Biol 2:584–590CrossRefGoogle Scholar
  95. 95.
    Hang HC, Wilson JP, Charron G (2011) Bioorthogonal chemical reporters for analyzing protein lipidation and lipid trafficking. Acc Chem Res 44:699–708CrossRefGoogle Scholar
  96. 96.
    Jao C, Roth M, Welti R, Salic A (2009) Metabolic labeling and direct imaging of choline phospholipids in vivo. Proc Natl Acad Sci USA 106:15332–15337CrossRefGoogle Scholar
  97. 97.
    Yount JS, Moltedo B, Yang Y-Y, Charron G, Moran TM, López CB, Hang HC (2010) Palmitoylome profiling reveals S-palmitoylation–dependent antiviral activity of IFITM3. Nat Chem Biol 6:610–614CrossRefGoogle Scholar
  98. 98.
    Peng T, Hang HC (2015) Bifunctional fatty acid chemical reporter for analyzing S-palmitoylated membrane protein-protein interactions in mammalian cells. J Am Chem Soc 137:556–559CrossRefGoogle Scholar
  99. 99.
    Niphakis MJ, Lum KM, Cognetta Iii AB, Correia BE, Ichu T-A, Olucha J, Brown SJ, Kundu S, Piscitelli F, Rosen H, Cravatt BF (2015) A global map of lipid-binding proteins and their ligandability in cells. Cell 161:1668–1680CrossRefGoogle Scholar
  100. 100.
    Haberkant P, Raijmakers R, Wildwater M, Sachsenheimer T, Brügger B, Maeda K, Houweling M, Gavin A-C, Schultz C, van Meer G, Heck AJR, Holthuis JCM (2013) In vivo profiling and visualization of cellular protein-lipid interactions using bifunctional fatty acids. Angew Chem Int Ed 52:4033–4038CrossRefGoogle Scholar
  101. 101.
    Hulce JJ, Cognetta AB, Niphakis MJ, Tully SE, Cravatt BF (2013) Proteome-wide mapping of cholesterol-interacting proteins in mammalian cells. Nat. Meth 10:259–264CrossRefGoogle Scholar
  102. 102.
    Salic A, Mitchison TJ (2008) A chemical method for fast and sensitive detection of DNA synthesis in vivo. Proc Natl Acad Sci USA 105:2415–2420CrossRefGoogle Scholar
  103. 103.
    Jao CY, Salic A (2008) Exploring RNA transcription and turnover in vivo by using click chemistry. Proc Natl Acad Sci USA 105:15779–15784CrossRefGoogle Scholar
  104. 104.
    Neef AB, Pernot L, Schreier VN, Scapozza L, Luedtke NW (2015) A bioorthogonal chemical reporter of viral infection. Angew Chem Int Ed 127:8022–8025CrossRefGoogle Scholar
  105. 105.
    Cravatt BF, Sorensen EJ (2000) Chemical strategies for the global analysis of protein function. Curr Opin Chem Biol 4:663–668CrossRefGoogle Scholar
  106. 106.
    Evans MJ, Cravatt BF (2006) Mechanism-based profiling of enzyme families. Chem Rev 106:3279–3301CrossRefGoogle Scholar
  107. 107.
    Sadaghiani AM, Verhelst SHL, Bogyo M (2007) Tagging and detection strategies for activity-based proteomics. Curr Opin Chem Biol 11:20–28CrossRefGoogle Scholar
  108. 108.
    Speers AE, Cravatt BF (2004) Profiling enzyme activities in vivo using click chemistry methods. Chem Biol 11:535–546CrossRefGoogle Scholar
  109. 109.
    Cravatt BF, Wright AT, Kozarich JW (2008) Activity-based protein profiling: from enzyme chemistry to proteomic chemistry. Annu Rev Biochem 77:383–414CrossRefGoogle Scholar
  110. 110.
    Fonović M, Bogyo M (2008) Activity-based probes as a tool for functional proteomic analysis of proteases. Expert Rev Proteomics 5:721–730CrossRefGoogle Scholar
  111. 111.
    Speers AE, Cravatt BF (2005) A tandem orthogonal proteolysis strategy for high-content chemical proteomics. J Am Chem Soc 127:10018–10019CrossRefGoogle Scholar
  112. 112.
    Weerapana E, Wang C, Simon GM, Richter F, Khare S, Dillon MBD, Bachovchin DA, Mowen K, Baker D, Cravatt BF (2010) Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature 468:790–795CrossRefGoogle Scholar
  113. 113.
    Sieber SA, Niessen S, Hoover HS, Cravatt BF (2006) Proteomic profiling of metalloprotease activities with cocktails of active-site probes. Nat Chem Biol 2:274–281CrossRefGoogle Scholar
  114. 114.
    Kalesh KA, Sim DSB, Wang J, Liu K, Lin Q, Yao SQ (2010) Small molecule probes that target Abl kinase. Chem Commun 46:1118–1120CrossRefGoogle Scholar
  115. 115.
    Salisbury CM, Cravatt BF (2007) Activity-based probes for proteomic profiling of histone deacetylase complexes. Proc Natl Acad Sci USA 104:1171–1176CrossRefGoogle Scholar
  116. 116.
    van Scherpenzeel M, van der Pot M, Arnusch CJ, Liskamp RMJ, Pieters RJ (2007) Detection of galectin-3 by novel peptidic photoprobes. Bioorg Med Chem Lett 17:376–378CrossRefGoogle Scholar
  117. 117.
    Tantama M, Lin W-C, Licht S (2008) An activity-based protein profiling probe for the nicotinic acetylcholine receptor. J Am Chem Soc 130:15766–15767CrossRefGoogle Scholar
  118. 118.
    Crump CJ, am Ende CW, Eric Ballard T, Pozdnyakov N, Pettersson M, Chau D-M, Bales KR, Li Y-M, Johnson DS (2012) Development of clickable active site-directed photoaffinity probes for γ-secretase. Bioorg Med Chem Lett 22:2997–3000CrossRefGoogle Scholar
  119. 119.
    Pozdnyakov N, Murrey HE, Crump CJ, Pettersson M, Ballard TE, am Ende CW, Ahn K, Li Y-M, Bales KR, Johnson DS (2013) γ-Secretase modulator (GSM) PHOTOAFFINITY probes reveal distinct allosteric binding sites on presenilin. J Biol Chem 288:9710–9720CrossRefGoogle Scholar
  120. 120.
    Zhang L, Chen X, Xue P, Sun HHY, Williams ID, Sharpless KB, Fokin VV, Jia G (2005) Ruthenium-catalyzed cycloaddition of alkynes and organic azides. J Am Chem Soc 127:15998–15999CrossRefGoogle Scholar
  121. 121.
    Boren BC, Narayan S, Rasmussen LK, Zhang L, Zhao H, Lin Z, Jia G, Fokin VV (2008) Ruthenium-catalyzed azide–alkyne cycloaddition: scope and mechanism. J Am Chem Soc 130:8923–8930CrossRefGoogle Scholar
  122. 122.
    Empting M, Avrutina O, Meusinger R, Fabritz S, Reinwarth M, Biesalski M, Voigt S, Buntkowsky G, Kolmar H (2011) “Triazole bridge”: disulfide-bond replacement by ruthenium-catalyzed formation of 1,5-disubstituted 1,2,3-triazoles. Angew Chem Int Ed 50:5207–5211CrossRefGoogle Scholar
  123. 123.
    Roice M, Johannsen I, Meldal M (2004) High capacity poly(ethylene glycol) based amino polymers for peptide and organic synthesis. QSAR Comb Sci 23:662–673CrossRefGoogle Scholar
  124. 124.
    Zhang J, Kemmink J, Rijkers DTS, Liskamp RMJ (2013) Synthesis of 1,5-triazole bridged vancomycin CDE-ring bicyclic mimics using RuAAC macrocyclization. Chem Commun 49:4498–4500CrossRefGoogle Scholar
  125. 125.
    McNulty J, Keskar K, Vemula R (2011) The first well-defined silver(I)-complex-catalyzed cycloaddition of azides onto terminal alkynes at room temperature. Chem Eur J 17:14727–14730CrossRefGoogle Scholar
  126. 126.
    McNulty J, Keskar K (2012) Discovery of a robust and efficient homogeneous silver(I) catalyst for the cycloaddition of azides onto terminal alkynes. Eur J Org Chem 2012:5462–5470CrossRefGoogle Scholar
  127. 127.
    Gao M, He C, Chen H, Bai R, Cheng B, Lei A (2013) Synthesis of pyrroles by click reaction: silver-catalyzed cycloaddition of terminal alkynes with isocyanides. Angew Chem Int Ed 52:6958–6961CrossRefGoogle Scholar
  128. 128.
    Horneff T, Chuprakov S, Chernyak N, Gevorgyan V, Fokin VV (2008) Rhodium-catalyzed transannulation of 1,2,3-triazoles with nitriles. J Am Chem Soc 130:14972–14974CrossRefGoogle Scholar
  129. 129.
    Rajasekar S, Anbarasan P (2014) Rhodium-catalyzed transannulation of 1,2,3-triazoles to polysubstituted pyrroles. J Org Chem 79:8428–8434CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Synthetic and Functional Biomolecule Center, College of Chemistry and Molecular EngineeringPeking UniversityBeijingChina
  2. 2.Peking-Tsinghua Center for Life SciencesBeijingChina

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