Topics in Current Chemistry

, 374:4 | Cite as

Cycloadditions for Studying Nucleic Acids

Review
Part of the following topical collections:
  1. Cycloadditions in Bioorthogonal Chemistry

Abstract

Cycloaddition reactions for site-specific or global modification of nucleic acids have enabled the preparation of a plethora of previously inaccessible DNA and RNA constructs for structural and functional studies on naturally occurring nucleic acids, the assembly of nucleic acid nanostructures, therapeutic applications, and recently, the development of novel aptamers. In this chapter, recent progress in nucleic acid functionalization via a range of different cycloaddition (click) chemistries is presented. At first, cycloaddition/click chemistries already used for modifying nucleic acids are summarized, ranging from the well-established copper(I)-catalyzed alkyne–azide cycloaddition reaction to copper free methods, such as the strain-promoted azide–alkyne cycloaddition, tetrazole-based photoclick chemistry and the inverse electron demand Diels–Alder cycloaddition reaction between strained alkenes and tetrazine derivatives. The subsequent sections contain selected applications of nucleic acid functionalization via click chemistry; in particular, site-specific enzymatic labeling in vitro, either via DNA and RNA recognizing enzymes or by introducing unnatural base pairs modified for click reactions. Further sections report recent progress in metabolic labeling and fluorescent detection of DNA and RNA synthesis in vivo, click nucleic acid ligation, click chemistry in nanostructure assembly and click-SELEX as a novel method for the selection of aptamers.

Keywords

Nucleic acid Cycloaddition Click chemistry CuAAC iEDDA Metabolic labeling 

References

  1. 1.
    Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem 40(11):2004–2021CrossRefGoogle Scholar
  2. 2.
    El-Sagheer AH, Brown T (2010) Click chemistry with DNA. Chem Soc Rev 39(4):1388–1405. doi: 10.1039/b901971p CrossRefGoogle Scholar
  3. 3.
    Paredes E, Das SR (2011) Click chemistry for rapid labeling and ligation of RNA. Chembiochem 12(1):125–131. doi: 10.1002/cbic.201000466 CrossRefGoogle Scholar
  4. 4.
    Gramlich PM, Wirges CT, Gierlich J, Carell T (2008) Synthesis of modified DNA by PCR with alkyne-bearing purines followed by a click reaction. Org Lett 10(2):249–251. doi: 10.1021/ol7026015 CrossRefGoogle Scholar
  5. 5.
    Gutsmiedl K, Fazio D, Carell T (2010) High-density DNA functionalization by a combination of Cu-catalyzed and Cu-free click chemistry. Chemistry 16(23):6877–6883. doi: 10.1002/chem.201000363 CrossRefGoogle Scholar
  6. 6.
    Weisbrod SH, Marx A (2007) A nucleoside triphosphate for site-specific labelling of DNA by the Staudinger ligation. Chem Commun 18:1828–1830. doi: 10.1039/b618257g CrossRefGoogle Scholar
  7. 7.
    Winz ML, Samanta A, Benzinger D, Jäschke A (2012) Site-specific terminal and internal labeling of RNA by poly(A) polymerase tailing and copper-catalyzed or copper-free strain-promoted click chemistry. Nucleic Acids Res 40(10):e78. doi: 10.1093/nar/gks062 CrossRefGoogle Scholar
  8. 8.
    Qu D, Zhou L, Wang W, Wang Z, Wang G, Chi W, Zhang B (2013) 5-Ethynylcytidine as a new agent for detecting RNA synthesis in live cells by “click” chemistry. Anal Biochem 434(1):128–135. doi: 10.1016/j.ab.2012.11.023 CrossRefGoogle Scholar
  9. 9.
    Wenge U, Ehrenschwender T, Wagenknecht HA (2013) Synthesis of 2′-O-propargyl nucleoside triphosphates for enzymatic oligonucleotide preparation and “click” modification of DNA with Nile red as fluorescent probe. Bioconjug Chem 24(3):301–304. doi: 10.1021/bc300624m CrossRefGoogle Scholar
  10. 10.
    Ren X, Gerowska M, El-Sagheer AH, Brown T (2014) Enzymatic incorporation and fluorescent labelling of cyclooctyne-modified deoxyuridine triphosphates in DNA. Bioorg Med Chem 22(16):4384–4390. doi: 10.1016/j.bmc.2014.05.050 CrossRefGoogle Scholar
  11. 11.
    Samanta A, Krause A, Jäschke A (2014) A modified dinucleotide for site-specific RNA-labelling by transcription priming and click chemistry. Chem Commun 50(11):1313–1316. doi: 10.1039/c3cc46132g CrossRefGoogle Scholar
  12. 12.
    Gierlich J, Burley GA, Gramlich PM, Hammond DM, Carell T (2006) Click chemistry as a reliable method for the high-density postsynthetic functionalization of alkyne-modified DNA. Org Lett 8(17):3639–3642. doi: 10.1021/ol0610946 CrossRefGoogle Scholar
  13. 13.
    Gramlich PM, Warncke S, Gierlich J, Carell T (2008) Click–click–click: single to triple modification of DNA. Angew Chem 47(18):3442–3444. doi: 10.1002/anie.200705664 CrossRefGoogle Scholar
  14. 14.
    Holstein JM, Schulz D, Rentmeister A (2014) Bioorthogonal site-specific labeling of the 5′-cap structure in eukaryotic mRNAs. Chem Commun 50(34):4478–4481. doi: 10.1039/c4cc01549e CrossRefGoogle Scholar
  15. 15.
    Schulz D, Holstein JM, Rentmeister A (2013) A chemo-enzymatic approach for site-specific modification of the RNA cap. Angew Chem 52(30):7874–7878. doi: 10.1002/anie.201302874 CrossRefGoogle Scholar
  16. 16.
    Seidu-Larry S, Krieg B, Hirsch M, Helm M, Domingo O (2012) A modified guanosine phosphoramidite for click functionalization of RNA on the sugar edge. Chem Commun 48(89):11014–11016. doi: 10.1039/c2cc34015a CrossRefGoogle Scholar
  17. 17.
    Kumar R, El-Sagheer A, Tumpane J, Lincoln P, Wilhelmsson LM, Brown T (2007) Template-directed oligonucleotide strand ligation, covalent intramolecular DNA circularization and catenation using click chemistry. J Am Chem Soc 129(21):6859–6864. doi: 10.1021/ja070273v CrossRefGoogle Scholar
  18. 18.
    El-Sagheer AH, Kumar R, Findlow S, Werner JM, Lane AN, Brown T (2008) A very stable cyclic DNA miniduplex with just two base pairs. Chembiochem 9(1):50–52. doi: 10.1002/cbic.200700538 CrossRefGoogle Scholar
  19. 19.
    Kocalka P, El-Sagheer AH, Brown T (2008) Rapid and efficient DNA strand cross-linking by click chemistry. Chembiochem 9(8):1280–1285. doi: 10.1002/cbic.200800006 CrossRefGoogle Scholar
  20. 20.
    Rozkiewicz DI, Gierlich J, Burley GA, Gutsmiedl K, Carell T, Ravoo BJ, Reinhoudt DN (2007) Transfer printing of DNA by “click” chemistry. Chembiochem 8(16):1997–2002. doi: 10.1002/cbic.200700402 CrossRefGoogle Scholar
  21. 21.
    Fischler M, Simon U, Nir H, Eichen Y, Burley GA, Gierlich J, Gramlich PM, Carell T (2007) Formation of bimetallic Ag–Au nanowires by metallization of artificial DNA duplexes. Small 3(6):1049–1055. doi: 10.1002/smll.200600534 CrossRefGoogle Scholar
  22. 22.
    Chan TR, Hilgraf R, Sharpless KB, Fokin VV (2004) Polytriazoles as copper(I)-stabilizing ligands in catalysis. Org Lett 6(17):2853–2855. doi: 10.1021/ol0493094 CrossRefGoogle Scholar
  23. 23.
    Thyagarajan S, Murthy NN, Narducci Sarjeant AA, Karlin KD, Rokita SE (2006) Selective DNA strand scission with binuclear copper complexes: implications for an active Cu2–O2 species. J Am Chem Soc 128(21):7003–7008. doi: 10.1021/ja061014t CrossRefGoogle Scholar
  24. 24.
    Gogoi K, Mane MV, Kunte SS, Kumar VA (2007) A versatile method for the preparation of conjugates of peptides with DNA/PNA/analog by employing chemo-selective click reaction in water. Nucleic Acids Res 35(21):e139. doi: 10.1093/nar/gkm935 CrossRefGoogle Scholar
  25. 25.
    Brown SD, Graham D (2010) Conjugation of an oligonucleotide to Tat, a cell-penetrating peptide, via click chemistry. Tetrahedron Lett 51(38):5032–5034. doi: 10.1016/j.tetlet.2010.07.101 CrossRefGoogle Scholar
  26. 26.
    El-Sagheer AH, Brown T (2010) New strategy for the synthesis of chemically modified RNA constructs exemplified by hairpin and hammerhead ribozymes. Proc Natl Acad Sci USA 107(35):15329–15334. doi: 10.1073/pnas.1006447107 CrossRefGoogle Scholar
  27. 27.
    Frolow O, Endeward B, Schiemann O, Prisner TF, Engels JW (2008) Nitroxide spin labeled RNA for long range distance measurements by EPR–PELDOR. Nucleic Acids Symp Ser 52:153–154. doi: 10.1093/nass/nrn078 CrossRefGoogle Scholar
  28. 28.
    Piton N, Mu Y, Stock G, Prisner TF, Schiemann O, Engels JW (2007) Base-specific spin-labeling of RNA for structure determination. Nucleic Acids Res 35(9):3128–3143. doi: 10.1093/nar/gkm169 CrossRefGoogle Scholar
  29. 29.
    Piton N, Schiemann O, Mu Y, Stock G, Prisner T, Engels JW (2005) Synthesis of spin-labeled RNAs for long range distance measurements by peldor. Nucleosides Nucleotides Nucleic Acids 24(5–7):771–775CrossRefGoogle Scholar
  30. 30.
    Schiemann O, Weber A, Edwards TE, Prisner TF, Sigurdsson ST (2003) Nanometer distance measurements on RNA using PELDOR. J Am Chem Soc 125(12):3434–3435. doi: 10.1021/ja0274610 CrossRefGoogle Scholar
  31. 31.
    Ding P, Wunnicke D, Steinhoff HJ, Seela F (2010) Site-directed spin-labeling of DNA by the azide–alkyne ‘click’ reaction: nanometer distance measurements on 7-deaza-2′-deoxyadenosine and 2′-deoxyuridine nitroxide conjugates spatially separated or linked to a ‘dA–dT’ base pair. Chemistry 16(48):14385–14396. doi: 10.1002/chem.201001572 CrossRefGoogle Scholar
  32. 32.
    Jakobsen U, Shelke SA, Vogel S, Sigurdsson ST (2010) Site-directed spin-labeling of nucleic acids by click chemistry: detection of abasic sites in duplex DNA by EPR spectroscopy. J Am Chem Soc 132(30):10424–10428. doi: 10.1021/ja102797k CrossRefGoogle Scholar
  33. 33.
    Wada T, Mochizuki A, Higashiya S, Tsuruoka H, S-i Kawahara, Ishikawa M, Sekine M (2001) Synthesis and properties of 2-azidodeoxyadenosine and its incorporation into oligodeoxynucleotides. Tetrahedron Lett 42(52):9215–9219. doi: 10.1016/S0040-4039(01)02028-7 CrossRefGoogle Scholar
  34. 34.
    Pourceau G, Meyer A, Vasseur JJ, Morvan F (2009) Azide solid support for 3′-conjugation of oligonucleotides and their circularization by click chemistry. J Organ Chem 74(17):6837–6842. doi: 10.1021/jo9014563 CrossRefGoogle Scholar
  35. 35.
    Neef AB, Luedtke NW (2014) An azide-modified nucleoside for metabolic labeling of DNA. Chembiochem 15(6):789–793. doi: 10.1002/cbic.201400037 CrossRefGoogle Scholar
  36. 36.
    Kiviniemi A, Virta P, Lonnberg H (2008) Utilization of intrachain 4′-C-azidomethylthymidine for preparation of oligodeoxyribonucleotide conjugates by click chemistry in solution and on a solid support. Bioconjug Chem 19(8):1726–1734. doi: 10.1021/bc800221p CrossRefGoogle Scholar
  37. 37.
    Aigner M, Hartl M, Fauster K, Steger J, Bister K, Micura R (2011) Chemical synthesis of site-specifically 2′-azido-modified RNA and potential applications for bioconjugation and RNA interference. Chembiochem 12(1):47–51. doi: 10.1002/cbic.201000646 CrossRefGoogle Scholar
  38. 38.
    Fauster K, Hartl M, Santner T, Aigner M, Kreutz C, Bister K, Ennifar E, Micura R (2012) 2′-Azido RNA, a versatile tool for chemical biology: synthesis, X-ray structure, siRNA applications, click labeling. ACS Chem Biol 7(3):581–589. doi: 10.1021/cb200510k CrossRefGoogle Scholar
  39. 39.
    Santner T, Hartl M, Bister K, Micura R (2014) Efficient access to 3′-terminal azide-modified RNA for inverse click-labeling patterns. Bioconjug Chem 25(1):188–195. doi: 10.1021/bc400513z CrossRefGoogle Scholar
  40. 40.
    Saxon E, Bertozzi CR (2000) Cell surface engineering by a modified Staudinger reaction. Science 287(5460):2007–2010CrossRefGoogle Scholar
  41. 41.
    Wang CC, Seo TS, Li Z, Ruparel H, Ju J (2003) Site-specific fluorescent labeling of DNA using Staudinger ligation. Bioconjug Chem 14(3):697–701. doi: 10.1021/bc0256392 CrossRefGoogle Scholar
  42. 42.
    Weisbrod SH, Baccaro A, Marx A (2008) DNA conjugation by Staudinger ligation. Nucleic Acids Symp Ser 52:383–384. doi: 10.1093/nass/nrn195 CrossRefGoogle Scholar
  43. 43.
    Weisbrod SH, Baccaro A, Marx A (2011) Site-specific DNA labeling by Staudinger ligation. Methods Mol Biol 751:195–207. doi: 10.1007/978-1-61779-151-2_12 CrossRefGoogle Scholar
  44. 44.
    Seela F, Pujari SS (2010) Azide–alkyne “click” conjugation of 8-aza-7-deazaadenine-DNA: synthesis, duplex stability, and fluorogenic dye labeling. Bioconjug Chem 21(9):1629–1641. doi: 10.1021/bc100090y CrossRefGoogle Scholar
  45. 45.
    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(47):16893–16899. doi: 10.1021/ja106553e CrossRefGoogle Scholar
  46. 46.
    Kennedy DC, McKay CS, Legault MC, 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(44):17993–18001. doi: 10.1021/ja2083027 CrossRefGoogle Scholar
  47. 47.
    Eltepu L, Jayaraman M, Rajeev KG, Manoharan M (2013) An immobilized and reusable Cu(I) catalyst for metal ion-free conjugation of ligands to fully deprotected oligonucleotides through click reaction. Chem Commun 49(2):184–186. doi: 10.1039/c2cc36811k CrossRefGoogle Scholar
  48. 48.
    Jewett JC, Sletten EM, Bertozzi CR (2010) Rapid Cu-free click chemistry with readily synthesized biarylazacyclooctynones. J Am Chem Soc 132(11):3688–3690. doi: 10.1021/ja100014q CrossRefGoogle Scholar
  49. 49.
    Chang PV, Prescher JA, Sletten EM, Baskin JM, Miller IA, Agard NJ, Lo A, Bertozzi CR (2010) Copper-free click chemistry in living animals. Proc Natl Acad Sci USA 107(5):1821–1826. doi: 10.1073/pnas.0911116107 CrossRefGoogle Scholar
  50. 50.
    van Delft P, Meeuwenoord NJ, Hoogendoorn S, Dinkelaar J, Overkleeft HS, van der Marel GA, Filippov DV (2010) Synthesis of oligoribonucleic acid conjugates using a cyclooctyne phosphoramidite. Org Lett 12(23):5486–5489. doi: 10.1021/ol102357u CrossRefGoogle Scholar
  51. 51.
    Singh I, Freeman C, Madder A, Vyle JS, Heaney F (2012) Fast RNA conjugations on solid phase by strain-promoted cycloadditions. Org Biomol Chem 10(33):6633–6639. doi: 10.1039/c2ob25628b CrossRefGoogle Scholar
  52. 52.
    Jayaprakash KN, Peng CG, Butler D, Varghese JP, Maier MA, Rajeev KG, Manoharan M (2010) Non-nucleoside building blocks for copper-assisted and copper-free click chemistry for the efficient synthesis of RNA conjugates. Org Lett 12(23):5410–5413. doi: 10.1021/ol102205j CrossRefGoogle Scholar
  53. 53.
    Shelbourne M, Chen X, Brown T, El-Sagheer AH (2011) Fast copper-free click DNA ligation by the ring-strain promoted alkyne–azide cycloaddition reaction. Chem Commun 47(22):6257–6259. doi: 10.1039/c1cc10743g CrossRefGoogle Scholar
  54. 54.
    Shelbourne M, Brown T Jr, El-Sagheer AH, Brown T (2012) Fast and efficient DNA crosslinking and multiple orthogonal labelling by copper-free click chemistry. Chem Commun 48(91):11184–11186. doi: 10.1039/c2cc35084j CrossRefGoogle Scholar
  55. 55.
    Marks IS, Kang JS, Jones BT, Landmark KJ, Cleland AJ, Taton TA (2011) Strain-promoted “click” chemistry for terminal labeling of DNA. Bioconjug Chem 22(7):1259–1263. doi: 10.1021/bc1003668 CrossRefGoogle Scholar
  56. 56.
    Jawalekar AM, Malik S, Verkade JM, Gibson B, Barta NS, Hodges JC, Rowan A, van Delft FL (2013) Oligonucleotide tagging for copper-free click conjugation. Molecules 18(7):7346–7363. doi: 10.3390/molecules18077346 CrossRefGoogle Scholar
  57. 57.
    Heuer-Jungemann A, Kirkwood R, El-Sagheer AH, Brown T, Kanaras AG (2013) Copper-free click chemistry as an emerging tool for the programmed ligation of DNA-functionalised gold nanoparticles. Nanoscale 5(16):7209–7212. doi: 10.1039/c3nr02362a CrossRefGoogle Scholar
  58. 58.
    Debets MF, van Berkel SS, Dommerholt J, Dirks AT, Rutjes FP, van Delft FL (2011) Bioconjugation with strained alkenes and alkynes. Acc Chem Res 44(9):805–815. doi: 10.1021/ar200059z CrossRefGoogle Scholar
  59. 59.
    Stubinitzky C, Cserep GB, Batzner E, Kele P, Wagenknecht HA (2014) 2′-Deoxyuridine conjugated with a reactive monobenzocyclooctyne as a DNA building block for copper-free click-type postsynthetic modification of DNA. Chem Commun 50(76):11218–11221. doi: 10.1039/c4cc02855d CrossRefGoogle Scholar
  60. 60.
    Gutsmiedl K, Wirges CT, Ehmke V, Carell T (2009) Copper-free “click” modification of DNA via nitrile oxide-norbornene 1,3-dipolar cycloaddition. Org Lett 11(11):2405–2408. doi: 10.1021/ol9005322 CrossRefGoogle Scholar
  61. 61.
    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(30):9654–9655. doi: 10.1021/ja803598e CrossRefGoogle Scholar
  62. 62.
    Arndt S, Wagenknecht HA (2014) “Photoclick” postsynthetic modification of DNA. Angew Chem 53(52):14580–14582. doi: 10.1002/anie.201407874 CrossRefGoogle Scholar
  63. 63.
    Sletten EM, Bertozzi CR (2009) Bioorthogonal chemistry: fishing for selectivity in a sea of functionality. Angew Chem 48(38):6974–6998. doi: 10.1002/anie.200900942 CrossRefGoogle Scholar
  64. 64.
    Schoch J, Staudt M, Samanta A, Wiessler M, Jäschke A (2012) Site-specific one-pot dual labeling of DNA by orthogonal cycloaddition chemistry. Bioconjug Chem 23(7):1382–1386. doi: 10.1021/bc300181n CrossRefGoogle Scholar
  65. 65.
    Cole CM, Yang J, Šečkutė J, Devaraj NK (2013) Fluorescent live-cell imaging of metabolically incorporated unnatural cyclopropene–mannosamine derivatives. Chembiochem 14(2):205–208. doi: 10.1002/cbic.201200719 CrossRefGoogle Scholar
  66. 66.
    Devaraj NK, Weissleder R, Hilderbrand SA (2008) Tetrazine-based cycloadditions: application to pretargeted live cell imaging. Bioconjug Chem 19(12):2297–2299. doi: 10.1021/bc8004446 CrossRefGoogle Scholar
  67. 67.
    Devaraj NK, Upadhyay R, Haun JB, Hilderbrand SA, Weissleder R (2009) Fast and sensitive pretargeted labeling of cancer cells through a tetrazine/trans-cyclooctene cycloaddition. Angew Chem 48(38):7013–7016. doi: 10.1002/anie.200903233 CrossRefGoogle Scholar
  68. 68.
    Devaraj NK, Weissleder R (2011) Biomedical applications of tetrazine cycloadditions. Acc Chem Res 44(9):816–827. doi: 10.1021/ar200037t CrossRefGoogle Scholar
  69. 69.
    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(4):298–304. doi: 10.1038/nchem.1250 CrossRefGoogle Scholar
  70. 70.
    Kaya E, Vrabel M, Deiml C, Prill S, Fluxa VS, Carell T (2012) A genetically encoded norbornene amino acid for the mild and selective modification of proteins in a copper-free click reaction. Angew Chem Int Ed Engl 51(18):4466–4469. doi: 10.1002/anie.201109252 CrossRefGoogle Scholar
  71. 71.
    Liu DS, Tangpeerachaikul A, Selvaraj R, Taylor MT, Fox JM, Ting AY (2012) Diels–Alder cycloaddition for fluorophore targeting to specific proteins inside living cells. J Am Chem Soc 134(2):792–795. doi: 10.1021/ja209325n CrossRefGoogle Scholar
  72. 72.
    Blackman ML, Royzen M, Fox JM (2008) Tetrazine ligation: fast bioconjugation based on inverse-electron-demand Diels–Alder reactivity. J Am Chem Soc 130(41):13518–13519. doi: 10.1021/ja8053805 CrossRefGoogle Scholar
  73. 73.
    Devaraj NK, Hilderbrand S, Upadhyay R, Mazitschek R, Weissleder R (2010) Bioorthogonal turn-on probes for imaging small molecules inside living cells. Angew Chem 49(16):2869–2872. doi: 10.1002/anie.200906120 CrossRefGoogle Scholar
  74. 74.
    Carlson JC, Meimetis LG, Hilderbrand SA, Weissleder R (2013) BODIPY-tetrazine derivatives as superbright bioorthogonal turn-on probes. Angew Chem Int Ed Engl 52(27):6917–6920. doi: 10.1002/anie.201301100 CrossRefGoogle Scholar
  75. 75.
    Karver MR, Weissleder R, Hilderbrand SA (2011) Synthesis and evaluation of a series of 1,2,4,5-tetrazines for bioorthogonal conjugation. Bioconjug Chem 22(11):2263–2270. doi: 10.1021/bc200295y CrossRefGoogle Scholar
  76. 76.
    Schoch J, Wiessler M, Jäschke A (2010) Post-synthetic modification of DNA by inverse-electron-demand Diels–Alder reaction. J Am Chem Soc 132(26):8846–8847. doi: 10.1021/ja102871p CrossRefGoogle Scholar
  77. 77.
    Šečkutė J, Yang J, Devaraj NK (2013) Rapid oligonucleotide-templated fluorogenic tetrazine ligations. Nucleic Acids Res 41(15):e148. doi: 10.1093/nar/gkt540 CrossRefGoogle Scholar
  78. 78.
    Wang K, Wang D, Ji K, Chen W, Zheng Y, Dai C, Wang B (2014) Post-synthesis DNA modifications using a trans-cyclooctene click handle. Org Biomol Chem 13:909–915. doi: 10.1039/C4OB02031F CrossRefGoogle Scholar
  79. 79.
    Schoch J, Ameta S, Jäschke A (2011) Inverse electron-demand Diels–Alder reactions for the selective and efficient labeling of RNA. Chem Commun 47(46):12536–12537. doi: 10.1039/c1cc15476a CrossRefGoogle Scholar
  80. 80.
    Pyka AM, Domnick C, Braun F, Kath-Schorr S (2014) Diels–Alder cycloadditions on synthetic RNA in mammalian cells. Bioconjug Chem 25(8):1438–1443. doi: 10.1021/bc500302y CrossRefGoogle Scholar
  81. 81.
    Ameta S, Becker J, Jäschke A (2014) RNA-peptide conjugate synthesis by inverse-electron demand Diels–Alder reaction. Org Biomol Chem 12(26):4701–4707. doi: 10.1039/c4ob00076e CrossRefGoogle Scholar
  82. 82.
    Asare-Okai PN, Agustin E, Fabris D, Royzen M (2014) Site-specific fluorescence labelling of RNA using bio-orthogonal reaction of trans-cyclooctene and tetrazine. Chem Commun 50(58):7844–7847. doi: 10.1039/c4cc02435d CrossRefGoogle Scholar
  83. 83.
    Vranken C, Deen J, Dirix L, Stakenborg T, Dehaen W, Leen V, Hofkens J, Neely RK (2014) Super-resolution optical DNA Mapping via DNA methyltransferase-directed click chemistry. Nucleic Acids Res 42(7):e50. doi: 10.1093/nar/gkt1406 CrossRefGoogle Scholar
  84. 84.
    Motorin Y, Burhenne J, Teimer R, Koynov K, Willnow S, Weinhold E, Helm M (2011) Expanding the chemical scope of RNA: methyltransferases to site-specific alkynylation of RNA for click labeling. Nucleic Acids Res 39(5):1943–1952. doi: 10.1093/nar/gkq825 CrossRefGoogle Scholar
  85. 85.
    Tomkuviene M, Clouet-d’Orval B, Cerniauskas I, Weinhold E, Klimasauskas S (2012) Programmable sequence-specific click-labeling of RNA using archaeal box C/D RNP methyltransferases. Nucleic Acids Res 40(14):6765–6773. doi: 10.1093/nar/gks381 CrossRefGoogle Scholar
  86. 86.
    Holstein JM, Stummer D, Rentmeister A (2015) Enzymatic modification of 5′-capped RNA with a 4-vinylbenzyl group provides a platform for photoclick and inverse electron-demand Diels–Alder reaction. Chem Sci 6(2):1362–1369. doi: 10.1039/C4SC03182B CrossRefGoogle Scholar
  87. 87.
    Silverman SK, Baum DA (2009) Use of deoxyribozymes in RNA research. Methods Enzymol 469:95–117. doi: 10.1016/S0076-6879(09)69005-4 CrossRefGoogle Scholar
  88. 88.
    Büttner L, Javadi-Zarnaghi F, Höbartner C (2014) Site-specific labeling of RNA at internal ribose hydroxyl groups: terbium-assisted deoxyribozymes at work. J Am Chem Soc 136(22):8131–8137. doi: 10.1021/ja503864v CrossRefGoogle Scholar
  89. 89.
    El-Sagheer AH, Brown T (2012) Click nucleic acid ligation: applications in biology and nanotechnology. Acc Chem Res 45(8):1258–1267. doi: 10.1021/ar200321n CrossRefGoogle Scholar
  90. 90.
    Isobe H, Fujino T, Yamazaki N, Guillot-Nieckowski M, Nakamura E (2008) Triazole-linked analogue of deoxyribonucleic acid ((TL)DNA): design, synthesis, and double-strand formation with natural DNA. Org Lett 10(17):3729–3732. doi: 10.1021/ol801230k CrossRefGoogle Scholar
  91. 91.
    El-Sagheer AH, Brown T (2009) Synthesis and polymerase chain reaction amplification of DNA strands containing an unnatural triazole linkage. J Am Chem Soc 131(11):3958–3964. doi: 10.1021/ja8065896 CrossRefGoogle Scholar
  92. 92.
    Qiu J, El-Sagheer AH, Brown T (2013) Solid phase click ligation for the synthesis of very long oligonucleotides. Chem Commun 49(62):6959–6961. doi: 10.1039/c3cc42451k CrossRefGoogle Scholar
  93. 93.
    El-Sagheer AH, Sanzone AP, Gao R, Tavassoli A, Brown T (2011) Biocompatible artificial DNA linker that is read through by DNA polymerases and is functional in Escherichia coli. Proc Natl Acad Sci USA 108(28):11338–11343. doi: 10.1073/pnas.1101519108 CrossRefGoogle Scholar
  94. 94.
    Birts CN, Sanzone AP, El-Sagheer AH, Blaydes JP, Brown T, Tavassoli A (2014) Transcription of click-linked DNA in human cells. Angew Chem 53(9):2362–2365. doi: 10.1002/anie.201308691 CrossRefGoogle Scholar
  95. 95.
    Chen X, El-Sagheer AH, Brown T (2014) Reverse transcription through a bulky triazole linkage in RNA: implications for RNA sequencing. Chem Commun 50(57):7597–7600. doi: 10.1039/c4cc03027c CrossRefGoogle Scholar
  96. 96.
    Stark MR, Pleiss JA, Deras M, Scaringe SA, Rader SD (2006) An RNA ligase-mediated method for the efficient creation of large, synthetic RNAs. RNA 12(11):2014–2019. doi: 10.1261/rna.93506 CrossRefGoogle Scholar
  97. 97.
    Mattick JS, Makunin IV (2006) Non-coding RNA. Hum Mol Genet 15(Suppl 1):R17–R29. doi: 10.1093/hmg/ddl046 CrossRefGoogle Scholar
  98. 98.
    Morris KV, Mattick JS (2014) The rise of regulatory RNA. Nat Rev Genet 15(6):423–437. doi: 10.1038/nrg3722 CrossRefGoogle Scholar
  99. 99.
    Switzer C, Moroney SE, Benner SA (1989) Enzymatic incorporation of a new base pair into DNA and RNA. J Am Chem Soc 111(21):8322–8323. doi: 10.1021/ja00203a067 CrossRefGoogle Scholar
  100. 100.
    Switzer CY, Moroney SE, Benner SA (1993) Enzymic recognition of the base pair between isocytidine and isoguanosine. Biochemistry 32(39):10489–10496. doi: 10.1021/bi00090a027 CrossRefGoogle Scholar
  101. 101.
    Geyer CR, Battersby TR, Benner SA (2003) Nucleobase pairing in expanded Watson–Crick-like genetic information systems. Structure 11(12):1485–1498CrossRefGoogle Scholar
  102. 102.
    Moser MJ, Marshall DJ, Grenier JK, Kieffer CD, Killeen AA, Ptacin JL, Richmond CS, Roesch EB, Scherrer CW, Sherrill CB, Van Hout CV, Zanton SJ, Prudent JR (2003) Exploiting the enzymatic recognition of an unnatural base pair to develop a universal genetic analysis system. Clin Chem 49(3):407–414CrossRefGoogle Scholar
  103. 103.
    Johnson SC, Sherrill CB, Marshall DJ, Moser MJ, Prudent JR (2004) A third base pair for the polymerase chain reaction: inserting isoC and isoG. Nucleic Acids Res 32(6):1937–1941. doi: 10.1093/nar/gkh522 CrossRefGoogle Scholar
  104. 104.
    Yang Z, Sismour AM, Sheng P, Puskar NL, Benner SA (2007) Enzymatic incorporation of a third nucleobase pair. Nucleic Acids Res 35(13):4238–4249. doi: 10.1093/nar/gkm395 CrossRefGoogle Scholar
  105. 105.
    Hirao I, Mitsui T, Kimoto M, Yokoyama S (2007) Development of an unnatural base pair for efficient PCR amplification. Nucleic Acids Symp Ser 51:9–10. doi: 10.1093/nass/nrm005 CrossRefGoogle Scholar
  106. 106.
    Kimoto M, Kawai R, Mitsui T, Yokoyama S, Hirao I (2009) An unnatural base pair system for efficient PCR amplification and functionalization of DNA molecules. Nucleic Acids Res 37(2):e14. doi: 10.1093/nar/gkn956 CrossRefGoogle Scholar
  107. 107.
    Seo YJ, Hwang GT, Ordoukhanian P, Romesberg FE (2009) Optimization of an unnatural base pair toward natural-like replication. J Am Chem Soc 131(9):3246–3252. doi: 10.1021/ja807853m CrossRefGoogle Scholar
  108. 108.
    Yang Z, Chen F, Alvarado JB, Benner SA (2011) Amplification, mutation, and sequencing of a six-letter synthetic genetic system. J Am Chem Soc 133(38):15105–15112. doi: 10.1021/ja204910n CrossRefGoogle Scholar
  109. 109.
    Hirao I, Kimoto M (2012) Unnatural base pair systems toward the expansion of the genetic alphabet in the central dogma. Proc Jpn Acad Ser B Phys Biol Sci 88(7):345–367CrossRefGoogle Scholar
  110. 110.
    Yamashige R, Kimoto M, Takezawa Y, Sato A, Mitsui T, Yokoyama S, Hirao I (2012) Highly specific unnatural base pair systems as a third base pair for PCR amplification. Nucleic Acids Res 40(6):2793–2806. doi: 10.1093/nar/gkr1068 CrossRefGoogle Scholar
  111. 111.
    Li L, Degardin M, Lavergne T, Malyshev DA, Dhami K, Ordoukhanian P, Romesberg FE (2014) Natural-like replication of an unnatural base pair for the expansion of the genetic alphabet and biotechnology applications. J Am Chem Soc 136(3):826–829. doi: 10.1021/ja408814g CrossRefGoogle Scholar
  112. 112.
    Malyshev DA, Dhami K, Lavergne T, Chen T, Dai N, Foster JM, Correa IR Jr, Romesberg FE (2014) A semi-synthetic organism with an expanded genetic alphabet. Nature 509(7500):385–388. doi: 10.1038/nature13314 CrossRefGoogle Scholar
  113. 113.
    Matray TJ, Kool ET (1998) Selective and stable DNA base pairing without hydrogen bonds. J Am Chem Soc 120(24):6191–6192. doi: 10.1021/ja9803310 CrossRefGoogle Scholar
  114. 114.
    Matray TJ, Kool ET (1999) A specific partner for abasic damage in DNA. Nature 399(6737):704–708. doi: 10.1038/21453 CrossRefGoogle Scholar
  115. 115.
    Morales JC, Kool ET (2000) Importance of terminal base pair hydrogen-bonding in 3′-end proofreading by the Klenow fragment of DNA polymerase I. Biochemistry 39(10):2626–2632CrossRefGoogle Scholar
  116. 116.
    Betz K, Malyshev DA, Lavergne T, Welte W, Diederichs K, Dwyer TJ, Ordoukhanian P, Romesberg FE, Marx A (2012) KlenTaq polymerase replicates unnatural base pairs by inducing a Watson–Crick geometry. Nat Chem Biol 8(7):612–614. doi: 10.1038/nchembio.966 CrossRefGoogle Scholar
  117. 117.
    Betz K, Malyshev DA, Lavergne T, Welte W, Diederichs K, Romesberg FE, Marx A (2013) Structural insights into DNA replication without hydrogen bonds. J Am Chem Soc 135(49):18637–18643. doi: 10.1021/ja409609j CrossRefGoogle Scholar
  118. 118.
    Dhami K, Malyshev DA, Ordoukhanian P, Kubelka T, Hocek M, Romesberg FE (2014) Systematic exploration of a class of hydrophobic unnatural base pairs yields multiple new candidates for the expansion of the genetic alphabet. Nucleic Acids Res 42(16):10235–10244. doi: 10.1093/nar/gku715 CrossRefGoogle Scholar
  119. 119.
    Lavergne T, Degardin M, Malyshev DA, Quach HT, Dhami K, Ordoukhanian P, Romesberg FE (2013) Expanding the scope of replicable unnatural DNA: stepwise optimization of a predominantly hydrophobic base pair. J Am Chem Soc 135(14):5408–5419. doi: 10.1021/ja312148q CrossRefGoogle Scholar
  120. 120.
    Li Z, Lavergne T, Malyshev DA, Zimmermann J, Adhikary R, Dhami K, Ordoukhanian P, Sun Z, Xiang J, Romesberg FE (2013) Site-specifically arraying small molecules or proteins on DNA using an expanded genetic alphabet. Chemistry 19(42):14205–14209. doi: 10.1002/chem.201302496 CrossRefGoogle Scholar
  121. 121.
    Malyshev DA, Dhami K, Quach HT, Lavergne T, Ordoukhanian P, Torkamani A, Romesberg FE (2012) Efficient and sequence-independent replication of DNA containing a third base pair establishes a functional six-letter genetic alphabet. Proc Natl Acad Sci USA 109(30):12005–12010. doi: 10.1073/pnas.1205176109 CrossRefGoogle Scholar
  122. 122.
    Malyshev DA, Pfaff DA, Ippoliti SI, Hwang GT, Dwyer TJ, Romesberg FE (2010) Solution structure, mechanism of replication, and optimization of an unnatural base pair. Chemistry 16(42):12650–12659. doi: 10.1002/chem.201000959 CrossRefGoogle Scholar
  123. 123.
    Malyshev DA, Seo YJ, Ordoukhanian P, Romesberg FE (2009) PCR with an expanded genetic alphabet. J Am Chem Soc 131(41):14620–14621. doi: 10.1021/ja906186f CrossRefGoogle Scholar
  124. 124.
    Endo M, Mitsui T, Okuni T, Kimoto M, Hirao I, Yokoyama S (2004) Unnatural base pairs mediate the site-specific incorporation of an unnatural hydrophobic component into RNA transcripts. Bioorg Med Chem Lett 14(10):2593–2596. doi: 10.1016/j.bmcl.2004.02.072 CrossRefGoogle Scholar
  125. 125.
    Hikida Y, Kimoto M, Yokoyama S, Hirao I (2010) Site-specific fluorescent probing of RNA molecules by unnatural base-pair transcription for local structural conformation analysis. Nat Protoc 5(7):1312–1323. doi: 10.1038/nprot.2010.77 CrossRefGoogle Scholar
  126. 126.
    Hirao I, Kimoto M, Yamashige R (2012) Natural versus artificial creation of base pairs in DNA: origin of nucleobases from the perspectives of unnatural base pair studies. Acc Chem Res 45(12):2055–2065. doi: 10.1021/ar200257x CrossRefGoogle Scholar
  127. 127.
    Hirao I, Mitsui T, Kimoto M, Kawai R, Sato A, Yokoyama S (2005) Non-hydrogen-bonded base pairs for specific transcription. Nucleic Acids Symp Ser 49:33–34. doi: 10.1093/nass/49.1.33 CrossRefGoogle Scholar
  128. 128.
    Hirao I, Mitsui T, Kimoto M, Yokoyama S (2007) An efficient unnatural base pair for PCR amplification. J Am Chem Soc 129(50):15549–15555. doi: 10.1021/ja073830m CrossRefGoogle Scholar
  129. 129.
    Kimoto M, Kawai R, Mitsui T, Yokoyama S, Hirao I (2008) Efficient PCR amplification by an unnatural base pair system. Nucleic Acids Symp Ser 52:469–470. doi: 10.1093/nass/nrn238 CrossRefGoogle Scholar
  130. 130.
    Kimoto M, Kawai R, Mitsui T, Yokoyama S, Hirao I (2008) Sequences around the unnatural base pair in DNA templates for efficient replication. Nucleic Acids Symp Ser 52:457–458. doi: 10.1093/nass/nrn232 CrossRefGoogle Scholar
  131. 131.
    Kimoto M, Mitsui T, Yokoyama S, Hirao I (2010) A unique fluorescent base analogue for the expansion of the genetic alphabet. J Am Chem Soc 132(14):4988–4989. doi: 10.1021/ja100806c CrossRefGoogle Scholar
  132. 132.
    Mitsui T, Kimoto M, Harada Y, Sato A, Kitamura A, To T, Hirao I, Yokoyama S (2002) Enzymatic incorporation of an unnatural base pair between 4-propynyl-pyrrole-2-carbaldehyde and 9-methyl-imidazo [(4,5)-b]pyridine into nucleic acids. Nucleic Acids Res Suppl 2:219–220CrossRefGoogle Scholar
  133. 133.
    Mitsui T, Kimoto M, Harada Y, Yokoyama S, Hirao I (2005) An efficient unnatural base pair for a base-pair-expanded transcription system. J Am Chem Soc 127(24):8652–8658. doi: 10.1021/ja0425280 CrossRefGoogle Scholar
  134. 134.
    Ohtsuki T, Kimoto M, Ishikawa M, Mitsui T, Hirao I, Yokoyama S (2001) Unnatural base pairs for specific transcription. Proc Natl Acad Sci USA 98(9):4922–4925. doi: 10.1073/pnas.091532698 CrossRefGoogle Scholar
  135. 135.
    Ishizuka T, Kimoto M, Sato A, Hirao I (2012) Site-specific functionalization of RNA molecules by an unnatural base pair transcription system via click chemistry. Chem Commun 48(88):10835–10837. doi: 10.1039/c2cc36293g CrossRefGoogle Scholar
  136. 136.
    Kawai R, Kimoto M, Ikeda S, Mitsui T, Endo M, Yokoyama S, Hirao I (2005) Site-specific fluorescent labeling of RNA molecules by specific transcription using unnatural base pairs. J Am Chem Soc 127(49):17286–17295. doi: 10.1021/ja0542946 CrossRefGoogle Scholar
  137. 137.
    Kawai R, Kimoto M, Mitsui T, Yokoyama S, Hirao I (2004) Site-specific fluorescent labeling of RNA by a base-pair expanded transcription system. Nucleic Acids Symp Ser 48:35–36. doi: 10.1093/nass/48.1.35 CrossRefGoogle Scholar
  138. 138.
    Kimoto M, Hirao I (2010) Site-specific incorporation of extra components into RNA by transcription using unnatural base pair systems. Methods Mol Biol 634:355–369. doi: 10.1007/978-1-60761-652-8_25 CrossRefGoogle Scholar
  139. 139.
    Kimoto M, Kawai R, Mitsui T, Harada Y, Sato A, Yokoyama S, Hirao I (2005) Site-specific incorporation of fluorescent probes into RNA by specific transcription using unnatural base pairs. Nucleic Acids Symp Ser 49:287–288. doi: 10.1093/nass/49.1.287 CrossRefGoogle Scholar
  140. 140.
    Kimoto M, Sato A, Kawai R, Yokoyama S, Hirao I (2009) Site-specific incorporation of functional components into RNA by transcription using unnatural base pair systems. Nucleic Acids Symp Ser 53:73–74. doi: 10.1093/nass/nrp037 CrossRefGoogle Scholar
  141. 141.
    Kimoto M, Yamashige R, Yokoyama S, Hirao I (2012) PCR amplification and transcription for site-specific labeling of large RNA molecules by a two-unnatural-base-pair system. J Nucleic Acids 2012:230943. doi: 10.1155/2012/230943 CrossRefGoogle Scholar
  142. 142.
    Seo YJ, Matsuda S, Romesberg FE (2009) Transcription of an expanded genetic alphabet. J Am Chem Soc 131(14):5046–5047. doi: 10.1021/ja9006996 CrossRefGoogle Scholar
  143. 143.
    Seo YJ, Malyshev DA, Lavergne T, Ordoukhanian P, Romesberg FE (2011) Site-specific labeling of DNA and RNA using an efficiently replicated and transcribed class of unnatural base pairs. J Am Chem Soc 133(49):19878–19888. doi: 10.1021/ja207907d CrossRefGoogle Scholar
  144. 144.
    Domnick C, Eggert F, Kath-Schorr S (2015) Site-specific enzymatic introduction of a norbornene modified unnatural base into RNA and application in post-transcriptional labeling. Chem Commun 51(39):8253–8256. doi: 10.1039/c5cc01765c CrossRefGoogle Scholar
  145. 145.
    Moriyama K, Kimoto M, Mitsui T, Yokoyama S, Hirao I (2005) Site-specific biotinylation of RNA molecules by transcription using unnatural base pairs. Nucleic Acids Res 33(15):e129. doi: 10.1093/nar/gni128 CrossRefGoogle Scholar
  146. 146.
    Morohashi N, Kimoto M, Sato A, Kawai R, Hirao I (2012) Site-specific incorporation of functional components into RNA by an unnatural base pair transcription system. Molecules 17(3):2855–2876. doi: 10.3390/molecules17032855 CrossRefGoogle Scholar
  147. 147.
    Li Z, Cai H, Hassink M, Blackman ML, Brown RC, Conti PS, Fox JM (2010) Tetrazine-trans-cyclooctene ligation for the rapid construction of 18F labeled probes. Chem Commun 46(42):8043–8045. doi: 10.1039/c0cc03078c CrossRefGoogle Scholar
  148. 148.
    Seitchik JL, Peeler JC, Taylor MT, Blackman ML, Rhoads TW, Cooley RB, Refakis C, Fox JM, Mehl RA (2012) Genetically encoded tetrazine amino acid directs rapid site-specific in vivo bioorthogonal ligation with trans-cyclooctenes. J Am Chem Soc 134(6):2898–2901. doi: 10.1021/ja2109745 CrossRefGoogle Scholar
  149. 149.
    Schneider S, Gattner MJ, Vrabel M, Flügel V, Lopez-Carrillo V, Prill S, Carell T (2013) Structural insights into incorporation of norbornene amino acids for click modification of proteins. Chembiochem. doi: 10.1002/cbic.201300435 Google Scholar
  150. 150.
    Schulz D, Rentmeister A (2014) Current approaches for RNA labeling in vitro and in cells based on click reactions. Chembiochem 15(16):2342–2347. doi: 10.1002/cbic.201402240 CrossRefGoogle Scholar
  151. 151.
    Chadalavada DM, Gratton EA, Bevilacqua PC (2010) The human HDV-like CPEB3 ribozyme is intrinsically fast-reacting. Biochemistry 49(25):5321–5330. doi: 10.1021/bi100434c CrossRefGoogle Scholar
  152. 152.
    Someya T, Ando A, Kimoto M, Hirao I (2015) Site-specific labeling of RNA by combining genetic alphabet expansion transcription and copper-free click chemistry. Nucleic Acids Res. doi: 10.1093/nar/gkv638 Google Scholar
  153. 153.
    Salic A, Mitchison TJ (2008) A chemical method for fast and sensitive detection of DNA synthesis in vivo. Proc Natl Acad Sci USA 105(7):2415–2420. doi: 10.1073/pnas.0712168105 CrossRefGoogle Scholar
  154. 154.
    Chehrehasa F, Meedeniya AC, Dwyer P, Abrahamsen G, Mackay-Sim A (2009) EdU, a new thymidine analogue for labelling proliferating cells in the nervous system. J Neurosci Methods 177(1):122–130. doi: 10.1016/j.jneumeth.2008.10.006 CrossRefGoogle Scholar
  155. 155.
    Zeng C, Pan F, Jones LA, Lim MM, Griffin EA, Sheline YI, Mintun MA, Holtzman DM, Mach RH (2010) Evaluation of 5-ethynyl-2′-deoxyuridine staining as a sensitive and reliable method for studying cell proliferation in the adult nervous system. Brain Res 1319:21–32. doi: 10.1016/j.brainres.2009.12.092 CrossRefGoogle Scholar
  156. 156.
    Jao CY, Salic A (2008) Exploring RNA transcription and turnover in vivo by using click chemistry. Proc Natl Acad Sci USA 105(41):15779–15784. doi: 10.1073/pnas.0808480105 CrossRefGoogle Scholar
  157. 157.
    Diermeier-Daucher S, Clarke ST, Hill D, Vollmann-Zwerenz A, Bradford JA, Brockhoff G (2009) Cell type specific applicability of 5-ethynyl-2′-deoxyuridine (EdU) for dynamic proliferation assessment in flow cytometry. Cytometry Part A J Int Soc Anal Cytol 75(6):535–546. doi: 10.1002/cyto.a.20712 CrossRefGoogle Scholar
  158. 158.
    Ross HH, Rahman M, Levkoff LH, Millette S, Martin-Carreras T, Dunbar EM, Reynolds BA, Laywell ED (2011) Ethynyldeoxyuridine (EdU) suppresses in vitro population expansion and in vivo tumor progression of human glioblastoma cells. J Neurooncol 105(3):485–498. doi: 10.1007/s11060-011-0621-6 CrossRefGoogle Scholar
  159. 159.
    Zhao H, Halicka HD, Li J, Biela E, Berniak K, Dobrucki J, Darzynkiewicz Z (2013) DNA damage signaling, impairment of cell cycle progression, and apoptosis triggered by 5-ethynyl-2′-deoxyuridine incorporated into DNA. Cytometry Part A J Int Soc Anal Cytol 83(11):979–988. doi: 10.1002/cyto.a.22396 CrossRefGoogle Scholar
  160. 160.
    Neef AB, Luedtke NW (2011) Dynamic metabolic labeling of DNA in vivo with arabinosyl nucleosides. Proc Natl Acad Sci USA 108(51):20404–20409. doi: 10.1073/pnas.1101126108 CrossRefGoogle Scholar
  161. 161.
    Qu D, Wang G, Wang Z, Zhou L, Chi W, Cong S, Ren X, Liang P, Zhang B (2011) 5-Ethynyl-2′-deoxycytidine as a new agent for DNA labeling: detection of proliferating cells. Anal Biochem 417(1):112–121. doi: 10.1016/j.ab.2011.05.037 CrossRefGoogle Scholar
  162. 162.
    Guan L, van der Heijden GW, Bortvin A, Greenberg MM (2011) Intracellular detection of cytosine incorporation in genomic DNA by using 5-ethynyl-2′-deoxycytidine. Chembiochem 12(14):2184–2190. doi: 10.1002/cbic.201100353 CrossRefGoogle Scholar
  163. 163.
    Neef AB, Samain F, Luedtke NW (2012) Metabolic labeling of DNA by purine analogues in vivo. Chembiochem 13(12):1750–1753. doi: 10.1002/cbic.201200253 CrossRefGoogle Scholar
  164. 164.
    Wang IH, Suomalainen M, Andriasyan V, Kilcher S, Mercer J, Neef A, Luedtke NW, Greber UF (2013) Tracking viral genomes in host cells at single-molecule resolution. Cell Host Microbe 14(4):468–480. doi: 10.1016/j.chom.2013.09.004 CrossRefGoogle Scholar
  165. 165.
    Hagemeijer MC, Vonk AM, Monastyrska I, Rottier PJ, de Haan CA (2012) Visualizing coronavirus RNA synthesis in time by using click chemistry. J Virol 86(10):5808–5816. doi: 10.1128/JVI.07207-11 CrossRefGoogle Scholar
  166. 166.
    Neef AB, Pernot L, Schreier VN, Scapozza L, Luedtke NW (2015) A bioorthogonal chemical reporter of viral infection. Angew Chem 54(27):7911–7914. doi: 10.1002/anie.201500250 CrossRefGoogle Scholar
  167. 167.
    Rieder U, Luedtke NW (2014) Alkene–tetrazine ligation for imaging cellular DNA. Angew Chem 53(35):9168–9172. doi: 10.1002/anie.201403580 CrossRefGoogle Scholar
  168. 168.
    Sawant AA, Tanpure AA, Mukherjee PP, Athavale S, Kelkar A, Galande S, Srivatsan SG (2015) A versatile toolbox for posttranscriptional chemical labeling and imaging of RNA. Nucleic Acids Res. doi: 10.1093/nar/gkv903 Google Scholar
  169. 169.
    Klug SJ, Famulok M (1994) All you wanted to know about SELEX. Mol Biol Rep 20(2):97–107CrossRefGoogle Scholar
  170. 170.
    Famulok M, Mayer G (2014) Aptamers and SELEX in chemistry and biology. Chem Biol 21(9):1055–1058. doi: 10.1016/j.chembiol.2014.08.003 CrossRefGoogle Scholar
  171. 171.
    Kimoto M, Yamashige R, Matsunaga K, Yokoyama S, Hirao I (2013) Generation of high-affinity DNA aptamers using an expanded genetic alphabet. Nat Biotechnol 31(5):453–457. doi: 10.1038/nbt.2556 CrossRefGoogle Scholar
  172. 172.
    Pinheiro VB, Taylor AI, Cozens C, Abramov M, Renders M, Zhang S, Chaput JC, Wengel J, Peak-Chew SY, McLaughlin SH, Herdewijn P, Holliger P (2012) Synthetic genetic polymers capable of heredity and evolution. Science 336(6079):341–344. doi: 10.1126/science.1217622 CrossRefGoogle Scholar
  173. 173.
    Vaught JD, Bock C, Carter J, Fitzwater T, Otis M, Schneider D, Rolando J, Waugh S, Wilcox SK, Eaton BE (2010) Expanding the chemistry of DNA for in vitro selection. J Am Chem Soc 132(12):4141–4151. doi: 10.1021/ja908035g CrossRefGoogle Scholar
  174. 174.
    Sefah K, Yang Z, Bradley KM, Hoshika S, Jimenez E, Zhang L, Zhu G, Shanker S, Yu F, Turek D, Tan W, Benner SA (2014) In vitro selection with artificial expanded genetic information systems. Proc Natl Acad Sci USA 111(4):1449–1454. doi: 10.1073/pnas.1311778111 CrossRefGoogle Scholar
  175. 175.
    Tolle F, Brandle GM, Matzner D, Mayer G (2015) A Versatile Approach Towards Nucleobase-Modified Aptamers. Angew Chem. doi: 10.1002/anie.201503652 Google Scholar
  176. 176.
    Lundberg EP, El-Sagheer AH, Kocalka P, Wilhelmsson LM, Brown T, Norden B (2010) A new fixation strategy for addressable nano-network building blocks. Chem Commun 46(21):3714–3716. doi: 10.1039/c001513j CrossRefGoogle Scholar
  177. 177.
    Qing G, Xiong H, Seela F, Sun T (2010) Spatially controlled DNA nanopatterns by “click” chemistry using oligonucleotides with different anchoring sites. J Am Chem Soc 132(43):15228–15232. doi: 10.1021/ja105246b CrossRefGoogle Scholar
  178. 178.
    Xiong H, Leonard P, Seela F (2012) Construction and assembly of branched Y-shaped DNA: “click” chemistry performed on dendronized 8-aza-7-deazaguanine oligonucleotides. Bioconjug Chem 23(4):856–870. doi: 10.1021/bc300013k CrossRefGoogle Scholar
  179. 179.
    Gerrard SR, Hardiman C, Shelbourne M, Nandhakumar I, Norden B, Brown T (2012) A new modular approach to nanoassembly: stable and addressable DNA nanoconstructs via orthogonal click chemistries. ACS Nano 6(10):9221–9228. doi: 10.1021/nn3035759 CrossRefGoogle Scholar
  180. 180.
    Cassinelli V, Oberleitner B, Sobotta J, Nickels P, Grossi G, Kempter S, Frischmuth T, Liedl T, Manetto A (2015) One-step formation of “chain-armor”-stabilized DNA nanostructures. Angew Chem 54(27):7795–7798. doi: 10.1002/anie.201500561 CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.LIMES Institute, Chemical Biology and Medicinal Chemistry UnitUniversity of BonnBonnGermany

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