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Modified Nucleic Acids pp 1–26Cite as

Emissive 5-Substituted Uridine Analogues

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Part of the book series: Nucleic Acids and Molecular Biology ((NUCLEIC,volume 31))

Abstract

Chemical biology and medicinal chemistry applications require new nucleoside analogues with well-defined photophysical properties in order to visualize, monitor, and advance the understanding of nucleic acids. To impart favorable photophysical properties upon the native nucleosides and decipher structure–property relationships, robust and flexible synthetic procedures are required. Modification at the 5-position of uridine likely comprises the largest number of chemical variations investigated to enhance and tune the photophysical properties of this practically non-emissive nucleoside. The chapter discusses the design, synthesis, and characterization of diverse emissive uridine analogues.

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References

  1. Peon J, Zewail AH (2001) DNA/RNA nucleotides and nucleosides: direct measurement of excited-state lifetime by femtosecond fluorescence up-conversion. Chem Phys Lett 348:255–262

    Article  CAS  Google Scholar 

  2. Munninger KO, Chang SH (1972) A fluorescent nucleoside from glutamic acid tRNA of Escherichia coli K 12. Biochem Biophys Commun 46:1837–1842

    Article  CAS  Google Scholar 

  3. Maelicke A, Vonderha F, Cramer F (1973) Spectroscopic properties of oligonucleotides excised from the anticodon region of phenylalanine tRNA from yeast. Biopolymers 12:27–43

    Article  CAS  PubMed  Google Scholar 

  4. Paszyc S, Rafalska M (1979) Photochemical properties of Yt base in aqueous solution. Nucleic Acids Res 6:385–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. McCloskey JA, Crain PF, Edmonds CG, Gupta R, Hashizume T, Phillipson DW, Stetter KO (1987) Structure determination of a new fluorescent tricyclic nucleoside from archaebacterial tRNA. Nucleic Acids Res 15:683–693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sinkeldam RW, Greco NJ, Tor Y (2010) Fluorescent analogs of biomolecular building blocks: design, properties, and applications. Chem Rev 110:2579–2619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Segal M, Fischer B (2012) Analogues of uracil nucleosides with intrinsic fluorescence (NIF-analogues): synthesis and photophysical properties. Org Biomol Chem 10:1571–1580

    Article  CAS  PubMed  Google Scholar 

  8. Greco NJ, Tor Y (2005) Simple fluorescent pyrimidine analogues detect the presence of DNA abasic sites. J Am Chem Soc 127:10784–10785

    Article  CAS  PubMed  Google Scholar 

  9. Crisp G, Flynn BL (1993) Palladium-catalyzed coupling of terminal alkynes with 5-(trifluoromethanesulfonyloxy)pyrimidine nucleosides. J Org Chem 58:6614–6619

    Article  CAS  Google Scholar 

  10. Ruth JL, Bergstrom DE (1976) Synthesis of C-5 substituted pyrimidine nucleosides via organopalladium intermediates. J Am Chem Soc 98:1587–1589

    Article  PubMed  Google Scholar 

  11. Ogino M, Yoshimura Y, Nazakawa A, Saito I, Fujimoto K (2005) Template-directed DNA photoligation via α-5-cyanovinyldeoxyuridine. Org Lett 7:2853–2856

    Article  CAS  PubMed  Google Scholar 

  12. Vorbrüggen H, Krolikiewicz K, Bennua B (1981) Nucleoside synthesis with trimethylsilyl triflate and perchlorate as catalyst. Chem Ber 114:1234–1255

    Article  Google Scholar 

  13. De Ornellas S, Williams TJ, Baumann CG, Fairlamb IJS (2013) Catalytic C–H/C–X bond functionalization of nucleosides, nucleotides, nucleic acids, amino acids, peptides and protein. In: Ribas X (ed) C–H/C–X bond functionalization: transition metal mediation, vol 11. RSC, Cambridge, pp 409–447

    Chapter  Google Scholar 

  14. Hayakawa H, Tanaka H, Obi K, Itoh M, Miyasaka T (1987) A simple and general entry to 5-substituted uridines based on the regioselective lithiation controlled by a protecting group in the sugar moiety. Tetrahedron Lett 28:87–90

    Article  CAS  Google Scholar 

  15. Noé MS, Ríos AC, Tor Y (2012) Design, synthesis, and spectroscopic properties of extended and fused pyrrolo-dC and pyrrolo-C analogs. Org Lett 14:3150–3153

    Article  PubMed  PubMed Central  Google Scholar 

  16. Xie Y, Dix AV, Tor Y (2009) FRET enabled real time detection of RNA-small molecule binding. J Am Chem Soc 131:17605–17614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tor Y, Del Valle S, Jaramillo D, Srivatsan SG, Ríos AC, Weizman H (2007) Designing new isomorphic fluorescent nucleobase analogues: the thieno[3,2-d]pyrimidine core. Tetrahedron 63:3608–3614

    Article  CAS  Google Scholar 

  18. Sinkeldam RW, Hopkins PA, Tor Y (2012) Modified 6-aza uridines: highly emissive pH-sensitive fluorescent nucleosides. ChemPhysChem 13:3350–3356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Moriguchi T, Ichimura M, Kato M, Suzuki K, Takahashi Y, Shinozuka K (2014) Development of the excimer probe responsible for DNA target bearing the silylated pyrenes at base moiety. Bioorg Med Chem Lett 24:4372–4375

    Article  CAS  PubMed  Google Scholar 

  20. Gias Uddin M, Moriguchi T, Ichimura M, Shinozuka K (2012) Synthesis and properties of molecular beacon DNA probe bearing novel silylated pyrene derivative. Key Eng Mater 497:47–50

    Article  Google Scholar 

  21. Sekhar Bag S, Kundu R, Matsumoto K, Saito Y, Saito I (2010) Singly and doubly labeled base-discriminating fluorescent oligonucleotide probes containing oxo-pyrene chromophore. Bioorg Med Chem Lett 20:3227–3230

    Article  Google Scholar 

  22. Sato Y, Moriguchi T, Shinozuka K (2012) Termini-free molecular beacon utilizing silylated perylene and anthraquinone attached to the C-5 position of pyrimidine nucleobase. Chem Lett 41:420–422

    Article  CAS  Google Scholar 

  23. Chowdhury JA, Moriguchi T, Shinozuka K (2015) Pseudo-dumbbell-type molecular beacon probes bearing modified deoxyuridine derivatives and a silylated pyrene as a fluorophore. Bull Chem Soc Jpn 88:496–502

    Article  CAS  Google Scholar 

  24. Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed 40:2004–2021

    Article  CAS  Google Scholar 

  25. Neef AB, Luedtke NW (2014) An azide-modified nucleoside for metabolic labeling of DNA. ChemBioChem 15:789–793

    Article  CAS  PubMed  Google Scholar 

  26. Jewett JC, Bertozzi CR (2010) Cu-free click cycloaddition reactions in chemical biology. Chem Soc Rev 39:1272–1279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ren X, Gerowska M, El-Sagheer AH, Brown T (2014) Enzymatic incorporation and fluorescent labeling of cyclooctyne-modified deoxyuridine triphosphates in DNA. Bioorg Med Chem 22:4384–4390

    Article  CAS  PubMed  Google Scholar 

  28. Stubinitzky C, Cserép GB, Bätzner E, Kele P, Wagenknecht H-A (2014) 2′-Deoxyuridine conjugated with a reactive monobenzocyclooctyne as a DNA building block for copper-free click-type postsynthetic modification of DNA. Chem Commun 50:11218–11221

    Article  CAS  Google Scholar 

  29. Beyer C, Wagenknecht H-A (2010) In situ azide formation and “click” reaction of nile red with DNA as an alternative postsynthetic route. Chem Commun 46:2230–2231

    Article  CAS  Google Scholar 

  30. 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 4:298–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 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 2012(51):4466–4469

    Article  Google Scholar 

  32. Devaraj NK, Weissleder R, Hilderbrand SA (2008) Tetrazine-based cycloadditions: application to pretargeted live cell imaging. Bioconjug Chem 19:2297–2299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Patterson DM, Nazarova LA, Xie B, Kamber DN, Prescher JA (2012) Functionalized cyclopropenes as bioorthogonal chemical reporters. J Am Chem Soc 134:18638–18643

    Article  CAS  PubMed  Google Scholar 

  34. Lang K, Davis L, Wallace S, Mahesh M, Cox DJ, Blackman ML, Fox JM, Chin JW (2012) Genetic encoding of bicyclononynes and trans-cyclooctenes for site-specific protein labeling in vitro and in live mammalian cells via rapid fluorogenic Diels–Alder reactions. J Am Chem Soc 134:10317–10320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Plass T, Milles S, Koehler C, Szymanski J, Mueller R, Wiessler M, Schultz C, Lemke EA (2012) Amino acids for Diels–Alder reactions in living cells. Angew Chem Int Ed 51:4166–4170

    Article  CAS  Google Scholar 

  36. Verri A, Focher F, Duncombe RJ, Basnak I, Walker RT, Coe PL, de Clercq E, Andrei G, Snoeck R, Balzarini J, Spadari S (2000) Anti-(herpes simplex virus) activity of 4′-thio-2′-deoxyuridines: a biochemical investigation for viral and cellular target enzymes. Biochem J 351(Pt 2):319–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rieder U, Luedtke NW (2014) Alkene-tetrazine ligation for imaging of cellular DNA. Angew Chem Int Ed 53:9168–9172

    Article  CAS  Google Scholar 

  38. Sanborn ME, Connolly BK, Gurunathan K, Levitus M (2007) Fluorescence properties and photophysics of the sulfoindocyanine Cy3 linked covalently to DNA. J Phys Chem B 111:11064–11074

    Article  CAS  PubMed  Google Scholar 

  39. Hall LM, Gerowska M, Brown T (2012) A highly fluorescent DNA toolkit: synthesis and properties of oligonucleotides containing new Cy3, Cy5 and Cy3B monomers. Nucleic Acids Res 40:e108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ryu JH, Heo JY, Bang E-K, Hwang GT, Kim BH (2012) Quencher-free linear beacon systems containing 2-ethynylfluorenone-labeled 2′-deoxyuridine units. Tetrahedron 68:72–78

    Article  CAS  Google Scholar 

  41. Lee J, Cho HY, Hwang GT (2013) Highly efficient quencher-free molecular beacon systems containing 2-ethynyldibenzofuran- and 2-ethynyldibenzothiophene-labeled 2′-deoxyuridine units. ChemBioChem 14:1353–1362

    Article  CAS  PubMed  Google Scholar 

  42. Tanaka M, Oguma K, Saito Y, Saito I (2012) Enhancement of fluorescence quenching and exciplex formation in DNA major groove by double incorporation of modified fluorescent deoxyuridines. Bioorg Med Chem Lett 22:4103–4105

    Article  CAS  PubMed  Google Scholar 

  43. Segal M, Yavin E, Kafri P, Shav-Tal Y, Fischer B (2013) Detection of mRNA of the cyclin D1 breast cancer marker by a novel duplex-DNA probe. J Med Chem 56:4860–4869

    Article  CAS  PubMed  Google Scholar 

  44. Tanpure AA, Srivatsan SG (2014) Synthesis, photophysical properties and incorporation of a highly emissive and environment-sensitive uridine analogue based on the Lucifer chromophore. ChemBioChem 15:1309–1316

    Article  CAS  PubMed  Google Scholar 

  45. Yuan L, Zhang Z, Xu X, Zhou X (2014) Chemical labeling of 5-iodo-2′-deoxyuridine with 4-ethynyl-N-ethyl-1,8-naphthalimide using copper-free Sonogashira cross-coupling in aqueous medium. Synthetic Commun 44:1007–1011

    Article  CAS  Google Scholar 

  46. Gondelaa A, Kumarb TS, Walczaka K, Wengel J (2010) Synthesis and biophysical properties of oligodeoxynucleotides containing 2′-deoxy-5-(4-nitro-1H-imidazol-1-yl)-β-D-uridine and 2′-deoxy-5-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-β-D-uridine monomers. Chem Biodivers 7:350–362

    Article  Google Scholar 

  47. Saito Y, Miyamoto S, Suzuki A, Matsumoto K, Ishihara T, Saito I (2012) Fluorescent nucleosides with ‘on–off’ switching function, pH-responsive fluorescent uridine derivatives. Bioorg Med Chem Lett 22:2753–2756

    Article  CAS  PubMed  Google Scholar 

  48. Barthes NPF, Karpenko IA, Dziuba D, Spadafora M, Auffret J, Demchenko AP, Mély Y, Benhida R, Michel BY, Burger A (2014) Development of environmentally sensitive fluorescent and dual emissive deoxyuridine analogues. RSC Adv 5:33536–33545

    Article  Google Scholar 

  49. Pawar MG, Nuthanakanti A, Srivatsan SG (2013) Heavy atom containing fluorescent ribonucleoside analog probe for the fluorescence detection of RNA-ligand binding. Bioconjugate Chem 24:1367–1377

    Article  CAS  Google Scholar 

  50. Tanpure AA, Srivatsan SG (2012) Synthesis and photophysical characterisation of a fluorescent nucleoside analogue that signals the presence of an abasic site in RNA. ChemBioChem 13:2392–2399

    Article  CAS  PubMed  Google Scholar 

  51. Kanamori T, Ohzeki H, Masaki Y, Ohkubo A, Takahashi M, Tsuda K, Ito T, Shirouzu M, Kuwasako K, Muto Y, Sekine M, Seio K (2015) Controlling the fluorescence of benzofuran-modified uracil residues in oligonucleotides by triple-helix formation. ChemBioChem 16:167–176

    Article  CAS  PubMed  Google Scholar 

  52. Pawar MG, Srivatsan SG (2011) Synthesis, photophysical characterization, and enzymatic incorporation of a microenvironment-sensitive fluorescent uridine analog. Org Lett 13:1114–1117

    Article  CAS  PubMed  Google Scholar 

  53. Pawar MG, Srivatsan SG (2013) Environment-responsive fluorescent nucleoside analogue probe for studying oligonucleotide dynamics in a model cell-like compartment. J Phys Chem B 117:14273–14282

    Article  CAS  PubMed  Google Scholar 

  54. Gutierrez AJ, Terhorst TJ, Matteucci MD, Froehler BC (1994) 5-Heteroaryl-2′-deoxyuridine analogs. Synthesis and incorporation into high-affinity oligonucleotides. J Am Chem Soc 116:5540–5544

    Article  CAS  Google Scholar 

  55. Wigerinck P, Pannecouque C, Snoeck R, Claes P, De Clercq E, Herdewijn P (1991) 5-(5-Bromothien-2-yl)-2′-deoxyuridine and 5-(5-chlorothien-2-yl)-2′-deoxyuridine are equipotent to (E)-5-(2-bromovinyl)-2′-deoxyuridine in the inhibition of herpes simplex virus type I replication. J Med Chem 34:2383–2389

    Article  CAS  PubMed  Google Scholar 

  56. Greco NJ, Tor Y (2007) Furan decorated nucleoside analogues as fluorescent probes: synthesis, photophysical evaluation, and site-specific incorporation. Tetrahedron 63:3515–3527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Sinkeldam RW, Wheat AJ, Boyaci H, Tor Y (2011) Emissive nucleosides as molecular rotors. ChemPhysChem 212:567–570

    Article  Google Scholar 

  58. Sinkeldam RW, Greco NJ, Tor Y (2008) Polarity of major grooves explored by using an isosteric emissive nucleoside. ChemBioChem 9:706–709

    Article  CAS  PubMed  Google Scholar 

  59. Greco NJ, Sinkeldam RW, Tor Y (2009) An emissive C analog distinguishes between G, 8-oxoG, and T. Org Lett 11:1115–1118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Srivatsan SG, Tor Y (2007) Fluorescent pyrimidine ribonucleotide: synthesis, enzymatic incorporation, and utilization. J Am Chem Soc 129:2044–2053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Srivatsan SG, Tor Y (2007) Using an emissive uridine analogue for assembling fluorescent HIV-1 TAR constructs. Tetrahedron 63:3601–3607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Lane RSK, Jones R, Sinkeldam RW, Tor Y, Magennis SW (2014) Two-photon-induced fluorescence of isomorphic nucleobase analogs. ChemPhysChem 15:867–871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Noé MS, Sinkeldam RW, Tor Y (2013) Oligodeoxynucleotides containing multiple thiophene-modified isomorphic fluorescent nucleosides. J Org Chem 78:8123–8128

    Article  PubMed  PubMed Central  Google Scholar 

  64. Hirose W, Sato K, Matsuda A (2011) Fluorescence properties of 5-(5,6-dimethoxybenzothiazol-2-yl)-2′-deoxyuridine (dbtU) and oligodeoxyribonucleotides containing dbtU. Eur J Org Chem 2011:6206–6217

    Article  CAS  Google Scholar 

  65. Sato K, Sasaki A, Matsuda A (2011) Highly fluorescent 5-(5,6-dimethoxybenzothiazol-2-yl)-2′-deoxyuridine 5′-triphosphate as an efficient substrate for DNA polymerases. ChemBioChem 12:2341–2346

    Article  CAS  PubMed  Google Scholar 

  66. Hirose W, Sato K, Matsuda A (2010) Selective detection of 5-formyl-2′-deoxyuridine, an oxidative lesion of thymidine, in DNA by a fluorogenic reagent. Angew Chem Int Ed 49:8392–8394

    Article  CAS  Google Scholar 

  67. Guo P, Xu X, Qiu X, Zhou Y, Yan S, Wang C, Lu C, Ma W, Weng X, Zhang X, Zhou X (2013) Synthesis and spectroscopic properties of fluorescent 5-benzimidazolyl-2′-deoxyuridines 5-fdU probes obtained from o-phenylenediamine derivatives. Org Biomol Chem 11:1610–1613

    Article  CAS  PubMed  Google Scholar 

  68. Clapham KM, Batsanov AS, Greenwood RDR, Bryce MR, Smith AE, Tarbit B (2008) Functionalized heteroarylpyridazines and pyridazin-3(2H)-one derivatives via palladium-catalyzed cross-coupling methodology. J Org Chem 73:2176–2181

    Article  CAS  PubMed  Google Scholar 

  69. Sinkeldam RW, Marcus P, Uchenik D, Tor Y (2011) Multisensing emissive pyrimidine. ChemPhysChem 12:2260–2265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Wanninger-Weiß C, Wagenknecht H-A (2007) Synthesis of 5-(2-pyrenyl)-2′-deoxyuridine as a DNA modification for electron-transfer studies: the critical role of the position of the chromophore attachment. Eur J Org Chem 1:64–71

    Google Scholar 

  71. Sekhar Bag S, Pradhan MK, Das SK, Jana S, Bag R (2014) Wavelength shifting oligonucleotide probe for the detection of adenosine of a target DNA with enhanced fluorescence signal. Bioorg Med Chem Lett 24:4678–4681

    Article  Google Scholar 

  72. Park SM, Nam S-J, Jeong HS, Kim WJ, Kim BH (2011) The effects of the 4-(4-methylpiperazine)phenyl group on nucleosides and oligonucleotides: cellular delivery, detection, and stability. Chem Asian J 6:487–492

    Article  CAS  PubMed  Google Scholar 

  73. Hopkins PA, Sinkeldam RW, Tor Y (2014) Visibly emissive and responsive extended 6-aza-uridines. Org Lett 16:5290–5293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Seela F, Chittepu P (2007) Oligonucleotides containing 6-aza-2′-deoxyuridine: synthesis, nucleobase protection, pH-dependent duplex stability, and metal-DNA formation. J Org Chem 72:4358–4366

    Article  CAS  PubMed  Google Scholar 

  75. Luyten I, Pankiewicz KW, Watanabe KA, Chattopadhyaya J (1998) Determination of the tautomeric equilibrium of Ψ-uridine in the basic solution. J Org Chem 63:1033–1040

    Article  CAS  Google Scholar 

  76. Lakowicz JR (2006) Principles of fluorescence spectroscopy. Springer, New York

    Book  Google Scholar 

  77. Okamoto A, Tainaka K, Saito I (2003) Clear distinction of purine bases on the complementary strand by a fluorescence change of a novel fluorescent nucleoside. J Am Chem Soc 125:4972–4973

    Article  CAS  PubMed  Google Scholar 

  78. Okamoto A, Kanatani K, Saito I (2004) Pyrene-labeled base-discriminating fluorescent DNA probes for homogeneous SNP typing. J Am Chem Soc 126:4820–4827

    Article  CAS  PubMed  Google Scholar 

  79. Okamoto A, Saito Y, Saito I (2005) Design of base-discriminating fluorescent nucleosides. J Photochem Photobiol C 6:108–122

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA

    Andrea Fin, Alexander R. Rovira, Patrycja A. Hopkins & Yitzhak Tor

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  1. Andrea Fin
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  2. Alexander R. Rovira
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  3. Patrycja A. Hopkins
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  4. Yitzhak Tor
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Correspondence to Yitzhak Tor .

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Editors and Affiliations

  1. The Institute of Scientific and Industri, Osaka University, Ibaraki, Osaka, Japan

    Kazuhiko Nakatani

  2. University of California, San Diego, La Jolla, California, USA

    Yitzhak Tor

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Fin, A., Rovira, A.R., Hopkins, P.A., Tor, Y. (2016). Emissive 5-Substituted Uridine Analogues. In: Nakatani, K., Tor, Y. (eds) Modified Nucleic Acids. Nucleic Acids and Molecular Biology, vol 31. Springer, Cham. https://doi.org/10.1007/978-3-319-27111-8_1

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