Skip to main content
SpringerLink
Log in

Polymerase Synthesis of Base-Modified DNA

  • Chapter
  • First Online:
Modified Nucleic Acids

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

Abstract

Enzymatic synthesis of base-modified DNA by polymerase incorporation of modified nucleotides is discussed. Modified 2′-deoxyribonucleoside triphosphates (dNTPs) are key substrates for polymerases and can be prepared either by triphosphorylation of modified nucleosides or by direct aqueous cross-coupling reactions of halogenated dNTPs with alkynes, arylboronic acids, or alkenes. The methods of polymerase synthesis include primer extension, PCR, nicking enzyme amplifications, and other methods which enable the synthesis of diverse types of long or short and double-stranded DNA or single-stranded oligonucleotides. The applications include labeling in diagnostics (labeling or coding of DNA bases) and chemical biology (bioconjugations, modulation of protein binding, etc.).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wilner OI, Wilner I (2012) Functionalized DNA nanostructures. Chem Rev 112:2528–2556. doi:10.1021/cr200104q

    Article  CAS  PubMed  Google Scholar 

  2. Clever GH, Kaul C, Carell T (2007) DNA-metal base pairs. Angew Chem Int Ed 46:6226–6236. doi:10.1002/anie.200701185

    Article  CAS  Google Scholar 

  3. Famulok M, Hartig JS, Mayer G (2007) Functional aptamers and aptazymes in biotechnology, diagnostics, and therapy. Chem Rev 107:3715–3743. doi:10.1021/cr0306743

    Article  CAS  PubMed  Google Scholar 

  4. Torring T, Voigt NV, Nangreave J et al (2011) DNA origami: a quantum leap for self-assembly of complex structures. Chem Soc Rev 40:5636–5646. doi:10.1039/c1cs15057j

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Caruthers MH (2013) The chemical synthesis of DNA/RNA: our gift to science. J Biol Chem 288:1420–1427. doi:10.1074/jbc.X112.442855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gierlich J, Burley GA, Gramlich PME et al (2006) Click chemistry as a reliable method for the high-density postsynthetic functionalization of alkyne-modified DNA. Org Lett 8:3639–3642. doi:10.1021/ol0610946

    Article  CAS  PubMed  Google Scholar 

  7. Seela F, Sirivolu VR, Chittepu P (2008) Modification of DNA with octadiynyl side chains: synthesis, base pairing, and formation of fluorescent coumarin dye conjugates of four nucleobases by the alkyne-azide “click” reaction. Bioconjugate Chem 19:211–224. doi:10.1021/bc700300f

    Article  CAS  Google Scholar 

  8. Shibata T, Glynn N, McMurry TBH et al (2006) Novel synthesis of O6-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT). Nucleic Acids Res 34:1884–1891. doi:10.1093/nar/gkl117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hentschel S, Alzeer J, Angelov T et al (2012) Synthesis of DNA interstrand cross-links using a photocaged nucleobase. Angew Chem Int Ed 51:3466–3469. doi:10.1002/anie.201108018

    Article  CAS  Google Scholar 

  10. Arndt S, Wagenknecht H (2014) “Photoclick” postsynthetic modification of DNA. Angew Chem 53:14580–14582. doi:10.1002/anie.201407874

    Article  CAS  Google Scholar 

  11. Gramlich PME, Wirges CT, Manetto A, Carell T (2008) Postsynthetic DNA modification through the copper-catalyzed azide-alkyne cycloaddition reaction. Angew Chem Int Ed 47:8350–8358. doi:10.1002/anie.200802077

    Article  CAS  Google Scholar 

  12. El-Sagheer AH, Brown T (2010) Click chemistry with DNA. Chem Soc Rev 39:1388–1405. doi:10.1039/b901971p

    Article  CAS  PubMed  Google Scholar 

  13. Rieder U, Luedtke NW (2014) Alkene-tetrazine ligation for imaging cellular DNA. Angew Chem Int Ed 53:9168–9172. doi:10.1002/anie.201403580

    Article  CAS  Google Scholar 

  14. Langer PR, Waldrop AA, Ward DC (1981) Enzymatic synthesis of biotin labeled polynucleotides: novel nucleic acid affinity probes. Proc Natl Acad Sci U S A 78:6633–6637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kuwahara M, Sugimoto N (2010) Molecular evolution of functional nucleic acids with chemical modifications. Molecules 15:5423–5444. doi:10.3390/molecules15085423

    Article  CAS  PubMed  Google Scholar 

  16. Hollenstein M (2012) Nucleoside triphosphates-building blocks for the modification of nucleic acids. Molecules 17:13569–13591. doi:10.3390/molecules171113569

    Article  CAS  PubMed  Google Scholar 

  17. Hocek M (2014) Synthesis of base-modified 2′-deoxyribonucleoside triphosphates and their use in enzymatic synthesis of modified DNA for applications in bioanalysis and chemical biology. J Org Chem 79:9914–9921. doi:10.1021/jo5020799

    Article  CAS  PubMed  Google Scholar 

  18. 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 88:345–367. doi:10.2183/pjab.88.345

    Article  CAS  Google Scholar 

  19. Hocek M, Fojta M (2008) Cross-coupling reactions of nucleoside triphosphates followed by polymerase incorporation. Construction and applications of base-functionalized nucleic acids. Org Biomol Chem 6:2233–2241. doi:10.1039/b803664k

    Article  CAS  PubMed  Google Scholar 

  20. Burgess K, Cook D (2000) Syntheses of nucleoside triphosphates. Chem Rev 100:2047–2059. doi:10.1021/cr990045m

    Article  CAS  PubMed  Google Scholar 

  21. Yoshikawa M, Kato T, Takenishi T (1967) A novel method for phosphorylation of nucleosides to 5′-nucleotides. Tetrahedron Lett 8:5065–5068

    Article  Google Scholar 

  22. Gillerman I, Fischer B (2010) An improved one-pot synthesis of nucleoside 5′-triphosphate analogues. Nucleosides Nucleotides Nucleic Acids 29:245–256. doi:10.1080/15257771003709569

    Article  CAS  PubMed  Google Scholar 

  23. Kuwahara M, Nagashima JI, Hasegawa M et al (2006) Systematic characterization of 2′-deoxynucleoside-5′-triphosphate analogs as substrates for DNA polymerases by polymerase chain reaction and kinetic studies on enzymatic production of modified DNA. Nucleic Acids Res 34:5383–5394. doi:10.1093/nar/gkl637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sakthivel K, Barbas CF (1998) Expanding the potential of DNA for binding and catalysis: highly functionalized dUTP derivatives that are substrates for thermostable DNA polymerases. Angew Chem Int Ed 37:2872–2875

    Article  CAS  Google Scholar 

  25. Thum O, Jäger S, Famulok M (2001) Functionalized DNA: a new replicable biopolymer. Angew Chem Int Ed 40:3990–3993

    Article  CAS  Google Scholar 

  26. Jäger S, Rasched G, Kornreich-Leshem H et al (2005) A versatile toolbox for variable DNA functionalization at high density. J Am Chem Soc 127:15071–15082. doi:10.1021/ja051725b

    Article  PubMed  CAS  Google Scholar 

  27. Lee SE, Sidorov A, Gourlain T et al (2001) Enhancing the catalytic repertoire of nucleic acids: a systematic study of linker length and rigidity by two modified triphosphates during PCR. Nucleic Acids Res 29:1565–1573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Seela F, Feiling E, Gross J et al (2001) Fluorescent DNA: the development of 7-deazapurine nucleoside triphosphates applicable for sequencing at the single molecule level. J Biotechnol 86:269–279. doi:10.1016/S0168-1656(00)00418-1

    Article  CAS  PubMed  Google Scholar 

  29. Roychowdhury A, Illangkoon H, Hendrickson CL, Benner SA (2004) 2′-deoxycytidines carrying amino and thiol functionality: synthesis and incorporation by vent (exo-)polymerase. Org Lett 6:489–492. doi:10.1021/ol0360290

    Article  CAS  PubMed  Google Scholar 

  30. Cheng Y, Dai C, Peng H et al (2011) Design, synthesis, and polymerase-catalyzed incorporation of click-modified boronic acid-TTP analogues. Chem Asian J 6:2747–2752. doi:10.1002/asia.201100229

    Article  CAS  PubMed  Google Scholar 

  31. Holzberger B, Marx A (2009) Enzymatic synthesis of perfluoroalkylated DNA. Bioorg Med Chem 17:3653–3658. doi:10.1016/j.bmc.2009.03.063

    Article  CAS  PubMed  Google Scholar 

  32. Wang Y, Tkachenko BA, Schreiner PR, Marx A (2011) Diamondoid-modified DNA. Org Biomol Chem 9:7482. doi:10.1039/c1ob05929g

    Article  CAS  PubMed  Google Scholar 

  33. Fujita H, Nakajima K, Kasahara Y et al (2015) Polymerase-mediated high-density incorporation of amphiphilic functionalities into DNA: enhancement of nuclease resistance and stability in human serum. Bioorg Med Chem Lett 25:333–336. doi:10.1016/j.bmcl.2014.11.037

    Article  CAS  PubMed  Google Scholar 

  34. Dziuba D, Pohl R, Hocek M (2015) Polymerase synthesis of DNA labelled with benzylidene cyanoacetamide-based fluorescent molecular rotors: fluorescent light-up probes for DNA-binding proteins. Chem Commun 51:4880–4882. doi:10.1039/c5cc00530b

    Article  CAS  Google Scholar 

  35. Baccaro A, Marx A (2010) Enzymatic synthesis of organic-polymer-grafted DNA. Chem Eur J 16:218–226. doi:10.1002/chem.200902296

    Article  CAS  PubMed  Google Scholar 

  36. Bußkamp H, Batroff E (2014) Efficient labelling of enzymatically synthesized vinyl-modified DNA by an inverse-electron-demand Diels–Alder reaction. Chem Commun 50:10827–10829. doi:10.1039/c4cc04332d

    Article  CAS  Google Scholar 

  37. Kuwahara M, Hanawa K, Ohsawa K et al (2006) Direct PCR amplification of various modified DNAs having amino acids: convenient preparation of DNA libraries with high-potential activities for in vitro selection. Bioorg Med Chem 14:2518–2526. doi:10.1016/j.bmc.2005.11.030

    Article  CAS  PubMed  Google Scholar 

  38. Baccaro A, Steck AL, Marx A (2012) Barcoded nucleotides. Angew Chem Int Ed 51:254–257. doi:10.1002/anie.201105717

    Article  CAS  Google Scholar 

  39. Verga D, Welter M, Steck AL, Marx A (2015) DNA polymerase-catalyzed incorporation of nucleotides modified with a G-quadruplex-derived DNAzyme. Chem Commun 51:7379–7381. doi:10.1039/c5cc01387a

    Article  CAS  Google Scholar 

  40. Ludwig J, Eckstein F (1989) Rapid and efficient synthesis of nucleoside 5′-O-(1-thiotriphosphates), 5′-triphosphates and 2′,3′-cyclophosphorothioates using 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one. J Org Chem 54:631–635. doi:10.1021/jo00264a024

    Article  CAS  Google Scholar 

  41. Caton-Williams J, Lin L, Smith M, Huang Z (2011) Convenient synthesis of nucleoside 5′-triphosphates for RNA transcription. Chem Commun 47:8142–8144. doi:10.1039/c1cc12201k

    Article  CAS  Google Scholar 

  42. Weizman H, Tor Y (2002) Redox-active metal-containing nucleotides: synthesis, tunability, and enzymatic incorporation into DNA. J Am Chem Soc 124:1568–1569. doi:10.1021/ja017193q

    Article  CAS  PubMed  Google Scholar 

  43. Hollenstein M (2013) Deoxynucleoside triphosphates bearing histamine, carboxylic acid, and hydroxyl residues—synthesis and biochemical characterization. Org Biomol Chem 11:5162–5172. doi:10.1039/c3ob40842f

    Article  CAS  PubMed  Google Scholar 

  44. Hollenstein M (2012) Synthesis of deoxynucleoside triphosphates that include proline, urea, or sulfonamide groups and their polymerase incorporation into DNA. Chem Eur J 18:13320–13330. doi:10.1002/chem.201201662

    Article  CAS  PubMed  Google Scholar 

  45. Obeid S, Yulikov M, Jeschke G, Marx A (2008) Enzymatic synthesis of multiple spin-labeled DNA. Angew Chem Int Ed 47:6782–6785. doi:10.1002/anie.200802314

    Article  CAS  Google Scholar 

  46. Genet JP, Savignac M (1999) Recent developments of palladium(0) catalyzed reactions in aqueous medium. J Organomet Chem 576:305–317

    Article  Google Scholar 

  47. Shaughnessy KH (2009) Hydrophilic ligands and their application in aqueous-phase metal-catalyzed reactions. Chem Rev 109:643–710. doi:10.1021/cr800403r

    Article  CAS  PubMed  Google Scholar 

  48. Western EC, Daft JR, Johnson EM et al (2003) Efficient one-step Suzuki arylation of unprotected halonucleosides, using water-soluble palladium catalysts. J Org Chem 68:6767–6774. doi:10.1021/jo034289p

    Article  CAS  PubMed  Google Scholar 

  49. Thoresen LH, Jiao G-S, Haaland WC et al (2003) Rigid, conjugated, fluoresceinated thymidine triphosphates: syntheses and polymerase mediated incorporation into DNA analogues. Chem Eur J 9:4603–4610. doi:10.1002/chem.200304944

    Article  CAS  PubMed  Google Scholar 

  50. Čapek P, Cahová H, Pohl R et al (2007) An efficient method for the construction of functionalized DNA bearing amino acid groups through cross-coupling reactions of nucleoside triphosphates followed by primer extension or PCR. Chem Eur J 13:6196–6203. doi:10.1002/chem.200700220

    Article  PubMed  CAS  Google Scholar 

  51. Vrábel M, Horáková P, Pivoňková H et al (2009) Base-modified DNA labeled by [Ru(bpy)3]2+ and [Os(bpy)3]2+ complexes: construction by polymerase incorporation of modified nucleoside triphosphates, electrochemical and luminescent properties, and applications. Chem Eur J 15:1144–1154. doi:10.1002/chem.200801538

    Article  PubMed  CAS  Google Scholar 

  52. Kielkowski P, Macíčková-Cahová H, Pohl R, Hocek M (2011) Transient and switchable (triethylsilyl)ethynyl protection of DNA against cleavage by restriction endonucleases. Angew Chem Int Ed 50:8727–8730. doi:10.1002/anie.201102898

    Article  CAS  Google Scholar 

  53. Riedl J, Ménová P, Pohl R et al (2012) GFP-like fluorophores as DNA labels for studying DNA-protein interactions. J Org Chem 77:8287–8293. doi:10.1021/jo301684b

    Article  CAS  PubMed  Google Scholar 

  54. Dadová J, Orság P, Pohl R et al (2013) Vinylsulfonamide and acrylamide modification of DNA for cross-linking with proteins. Angew Chem Int Ed 52:10515–10518. doi:10.1002/anie.201303577

    Article  CAS  Google Scholar 

  55. Balintová J, Pohl R, Horáková P et al (2011) Anthraquinone as a redox label for DNA: synthesis, enzymatic incorporation, and electrochemistry of anthraquinone-modified nucleosides, nucleotides, and DNA. Chem Eur J 17:14063–14073. doi:10.1002/chem.201101883

    Article  PubMed  CAS  Google Scholar 

  56. Hervé G, Sartori G, Enderlin G et al (2014) Palladium-catalyzed Suzuki reaction in aqueous solvents applied to unprotected nucleosides and nucleotides. RSC Adv 4:18558–18594. doi:10.1039/c3ra47911k

    Article  CAS  Google Scholar 

  57. Omumi A, Beach DG, Baker M et al (2011) Postsynthetic guanine arylation of DNA by Suzuki-Miyaura cross-coupling. J Am Chem Soc 133:42–50. doi:10.1021/ja106158b

    Article  CAS  PubMed  Google Scholar 

  58. Cahová H, Jäschke A (2013) Nucleoside-based diarylethene photoswitches and their facile incorporation into photoswitchable DNA. Angew Chem Int Ed 52:3186–3190. doi:10.1002/anie.201209943

    Article  CAS  Google Scholar 

  59. Lercher L, McGouran JF, Kessler BM et al (2013) DNA modification under mild conditions by Suzuki-Miyaura cross-coupling for the generation of functional probes. Angew Chem Int Ed 52:10553–10558. doi:10.1002/ange.201304038

    Article  CAS  Google Scholar 

  60. Čapek P, Pohl R, Hocek M (2006) Cross-coupling reactions of unprotected halopurine bases, nucleosides, nucleotides and nucleoside triphosphates with 4-borono-phenylalanine in water. Synthesis of (purin-8-yl)- and (purin-6-yl)phenylalanines. Org Biomol Chem 4:2278–2284. doi:10.1039/b604010a

    Article  PubMed  Google Scholar 

  61. Collier A, Wagner G (2006) A facile two-step synthesis of 8-arylated guanosine mono- and triphosphates (8-aryl GXPs). Org Biomol Chem 4:4526–4532. doi:10.1039/b614477b

    Article  CAS  PubMed  Google Scholar 

  62. Western EC, Shaughnessy KH (2005) Inhibitory effects of the guanine moiety on Suzuki couplings of unprotected halonucleosides in aqueous media. J Org Chem 70:6378–6388. doi:10.1021/jo050832l

    Article  CAS  PubMed  Google Scholar 

  63. Cahová H, Havran L, Brázdilová P et al (2008) Aminophenyl- and nitrophenyl-labeled nucleoside triphosphates: synthesis, enzymatic incorporation, and electrochemical detection. Angew Chem Int Ed 47:2059–2062. doi:10.1002/anie.200705088

    Article  CAS  Google Scholar 

  64. Horáková P, Macíčková-Cahová H, Pivoňková H et al (2011) Tail-labelling of DNA probes using modified deoxynucleotide triphosphates and terminal deoxynucleotidyl tranferase. Application in electrochemical DNA hybridization and protein-DNA binding assays. Org Biomol Chem 9:1366–1371. doi:10.1039/c3cc41438h

    Article  PubMed  CAS  Google Scholar 

  65. Ménová P, Cahová H, Plucnara M et al (2013) Polymerase synthesis of oligonucleotides containing a single chemically modified nucleobase for site-specific redox labelling. Chem Commun 49:4652–4654. doi:10.1039/c3cc41438h

    Article  CAS  Google Scholar 

  66. Raindlová V, Pohl R, Sanda M, Hocek M (2010) Direct polymerase synthesis of reactive aldehyde-functionalized DNA and its conjugation and staining with hydrazines. Angew Chem Int Ed 49:1064–1066. doi:10.1002/anie.200905556

    Article  CAS  Google Scholar 

  67. Riedl J, Pohl R, Rulíšek L, Hocek M (2012) Synthesis and photophysical properties of biaryl-substituted nucleos(t)ides. Polymerase synthesis of DNA probes bearing solvatochromic and pH-sensitive dual fluorescent and 19F NMR labels. J Org Chem 77:1026–1044. doi:10.1021/jo202321g

    Article  CAS  PubMed  Google Scholar 

  68. Balintová J, Plucnara M, Vidláková P et al (2013) Benzofurazane as a new redox label for electrochemical detection of DNA: towards multipotential redox coding of DNA bases. Chem Eur J 19:12720–12731. doi:10.1002/chem.201301868

    Article  PubMed  CAS  Google Scholar 

  69. Mačková M, Pohl R, Hocek M (2014) Polymerase synthesis of DNAs bearing vinyl groups in the major groove and their cleavage by restriction endonucleases. ChemBioChem 15:2306–2312. doi:10.1002/cbic.201402319

    Article  PubMed  CAS  Google Scholar 

  70. Heck RF (1979) Palladium-catalyzed reactions of organic halides with olefins. Acc Chem Res 12:146–151

    Article  CAS  Google Scholar 

  71. Beletskaya IP, Cheprakov AV (2000) The Heck reaction as a sharpening stone of palladium catalysis. Chem Rev 100:3009–3066. doi:10.1021/cr9903048

    Article  CAS  PubMed  Google Scholar 

  72. Agrofoglio LA, Gillaizeau I, Saito Y (2003) Palladium-assisted routes to nucleosides. Chem Rev 103:1875–1916. doi:10.1021/cr010374q

    Article  CAS  PubMed  Google Scholar 

  73. Tobrman T, Dvořák D (2008) Heck reactions of 6- and 2-halopurines. Eur J Org Chem 17:2923–2928. doi:10.1002/ejoc.200800091

    Article  CAS  Google Scholar 

  74. Kore AR, Shanmugasundaram M (2012) Highly stereoselective palladium-catalyzed Heck coupling of 5-iodouridine-5′-triphosphates with allylamine: a new efficient method for the synthesis of (E)-5-aminoallyl-uridine-5′-triphosphates. Tetrahedron Lett 53:2530–2532. doi:10.1016/j.tetlet.2012.03.018

    Article  CAS  Google Scholar 

  75. Dadova J, Pohl R, Fojta M, Hocek M (2013) Aqueous Heck cross-coupling preparation of acrylate-modified nucleotides and nucleoside triphosphates for polymerase synthesis of acrylate-labeled DNA. J Org Chem 78:9627–9637. doi:10.1021/jo4011574

    Article  CAS  PubMed  Google Scholar 

  76. Cahová H, Pohl R, Bednárová L, Nováková K (2008) Synthesis of 8-bromo-, 8-methyl-and 8-phenyl-dATP and their polymerase incorporation into DNA. Org Biomol Chem 6:3657–3660. doi:10.1039/B811935J

    Article  PubMed  CAS  Google Scholar 

  77. Siegmund V, Diederichsen U, Marx A (2012) Enzymatic synthesis of 8-vinyl-and 8-styryl-2′-deoxyguanosine modified DNA—novel fluorescent molecular probes. Bioorg Med Chem Lett 22:3136–3139. doi:10.1016/j.bmcl.2012.03.056

    Article  PubMed  CAS  Google Scholar 

  78. Pavlov YI, Minnick DT, Izuta S, Kunkel TA (1994) DNA replication fidelity with 8-oxodeoxyguanosine triphosphate. Biochemistry 33:4695–4701. doi:10.1021/bi00181a029

    Article  CAS  PubMed  Google Scholar 

  79. Morgues S, Trzcionka J, Vasseur JJ, Pratviel G, Meunier B (2008) Incorporation of oxidized guanine nucleoside 5′-triphosphates in DNA with DNA polymerases and preparation of single-lesion carrying DNA. Biochemistry 47:4788–4799. doi:10.1021/bi7022199

    Article  CAS  Google Scholar 

  80. Kamath-Loeb AS, Hizi A, Kasai H, Loeb LA (1997) Incorporation of the guanosine triphosphate analogs 8-oxo-dGTP and 8-NH2-dGTP by reverse transcriptases and mammalian DNA polymerases. J Biol Chem 47:4788–4799. doi:10.1074/jbc.272.9.5892

    Google Scholar 

  81. Lam C, Hipolito C, Perrin DM (2008) Synthesis and enzymatic incorporation of modified deoxyadenosine triphosphates. Eur J Org Chem 4915–4923. doi:10.1002/ejoc.200800381

    Google Scholar 

  82. Hollenstein M, Hipolito CJ, Lam CH (2009) A self-cleaving DNA enzyme modified with amines, guanidines and imidazoles operates independently of divalent metal cations (M2+). Nucleic Acids Res 5:1638–1649. doi:10.1093/nar/gkn1070

    Article  CAS  Google Scholar 

  83. Hipolito CJ, Hollenstein M, Lam CH (2011) Protein-inspired modified DNAzymes: dramatic effects of shortening side-chain length of 8-imidazolyl modified deoxyadenosines in selecting RNaseA mimicking DNAzymes. Org Biomol Chem 9:2266–2273. doi:10.1039/c1ob05359k

    Article  CAS  PubMed  Google Scholar 

  84. Ito J, Braithwaite DK (1991) Compilation and alignment of DNA polymerase sequences. Nucleic Acids Res 19:4045–4049. doi:10.1093/nar/19.15.4045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Filée J, Forterre P, Sen-Lin T, Laurent J (2002) Evolution of DNA polymerase families: evidences for multiple gene exchange between cellular and viral proteins. J Mol Evol 54:763–773. doi:10.1007/s00239-001-0078-x

    Article  PubMed  CAS  Google Scholar 

  86. Steitz TA (1999) DNA polymerases: structural diversity and common mechanisms. J Biol Chem 274:17395–17398. doi:10.1074/jbc.274.25.17395

    Article  CAS  PubMed  Google Scholar 

  87. Ramsay N, Jemth A-S, Brown A et al (2010) CyDNA: synthesis and replication of highly Cy-dye substituted DNA by an evolved polymerase. J Am Chem Soc 132:5096–5104. doi:10.1021/ja909180c

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Staiger N, Marx A (2010) A DNA polymerase with increased reactivity for ribonucleotides and C5‐modified deoxyribonucleotides. ChemBioChem 11:1963–1966. doi:10.1002/cbic.201000384

    Article  CAS  PubMed  Google Scholar 

  89. Brázdilová P, Vrábel M, Pohl R, Pivoňková H et al (2007) Ferrocenylethynyl derivatives of nucleoside triphosphates: synthesis, incorporation, electrochemistry, and bioanalytical applications. Chem Eur J 13:9527–9533. doi:10.1002/chem.200701249

    Article  PubMed  CAS  Google Scholar 

  90. Li H, Peng X, Seela F (2004) Fluorescence quenching of parallel-stranded DNA bound ethidium bromide: the effect of 7-deaza-2′-deoxyisoguanosine and 7-halogenated derivatives. Bioorg Med Chem Lett 14:6031–6034. doi:10.1016/j.bmcl.2004.09.071

    Article  CAS  PubMed  Google Scholar 

  91. Seela F, Sirivolu VR, Chittepu P (2007) Modification of DNA with octadiynyl side chains: synthesis, base pairing, and formation of fluorescent coumarin dye conjugates of four nucleobases by the alkyne-azide “click” reaction. Bioconjugate Chem 19:211–224. doi:10.1021/bc700300f

    Article  CAS  Google Scholar 

  92. Ménová P, Dziuba D, Güixens-Gallardo P et al (2015) Fluorescence quenching in oligonucleotides containing 7-substituted 7-deazaguanine bases prepared by the nicking enzyme amplification reaction. Bioconjugate Chem 26:361–366. doi:10.1021/acs.bioconjchem.5b00006

    Article  CAS  Google Scholar 

  93. Ménová P, Hocek M (2012) Preparation of short cytosine-modified oligonucleotides by nicking enzyme amplification reaction. Chem Commun 48:6921–6923. doi:10.1039/C2CC32930A

    Article  CAS  Google Scholar 

  94. Ménová P, Raindlová V, Hocek M (2013) Scope and limitations of the nicking enzyme amplification reaction for the synthesis of base-modified oligonucleotides and primers for PCR. Bioconjugate Chem 24:1081–1093. doi:10.1021/bc400149q

    Article  CAS  Google Scholar 

  95. Dziuba D, Pohl R, Hocek M (2014) Bodipy-labeled nucleoside triphosphates for polymerase synthesis of fluorescent DNA. Bioconjugate Chem 25:1984–1995. doi:10.1021/bc5003554

    Article  CAS  Google Scholar 

  96. Jäger S, Famulok M (2004) Generation and enzymatic amplification of high‐density functionalized DNA double strands. Angew Chem Int Ed 43:3337–3340. doi:10.1002/anie.200453926

    Article  Google Scholar 

  97. Kielkowski P, Fanfrlík J, Hocek M (2014) 7‐Aryl‐7‐deazaadenine 2′‐deoxyribonucleoside triphosphates (dNTPs): better substrates for DNA polymerases than dATP in competitive incorporations. Angew Chem Int Ed 53:7552–7555. doi:10.1002/anie.201404742

    Article  CAS  Google Scholar 

  98. Sinkeldam RW, Greco NJ, Tor Y (2010) Fluorescent analogs of biomolecular building blocks: design, properties, and applications. Chem Rev 110:2579–2619. doi:10.1021/cr900301e

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Tanpure AA, Pawar MG, Srivatsan SG (2013) Fluorescent nucleoside analogs: probes for investigating nucleic acid structure and function. Isr J Chem 53:366–378. doi:10.1002/ijch.201300010

    Article  CAS  Google Scholar 

  100. Palecek E, Bartosik M (2012) Electrochemistry of nucleic acids. Chem Rev 112:3427–3481. doi:10.1021/cr200303p

    Article  CAS  PubMed  Google Scholar 

  101. Balintová J, Špaček J, Pohl R, Brázdová M et al (2015) Azidophenyl as a click-transformable redox label of DNA suitable for electrochemical detection of DNA–protein interactions. Chem Sci 6:575–587. doi:10.1039/C4SC01906G

    Article  CAS  Google Scholar 

  102. Prober JM, Trainor GL, Dam RJ, Hobbs FW et al (1987) A system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotides. Science 238:336–341. doi:10.1126/science.2443975

    Article  CAS  PubMed  Google Scholar 

  103. Turcatti G, Romieu A, Fedurco M, Tairi AP (2008) A new class of cleavable fluorescent nucleotides: synthesis and optimization as reversible terminators for DNA sequencing by synthesis. Nucleic Acids Res 36:e25. doi:10.1093/nar/gkn021

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Riedl J, Pohl R, Ernsting NP et al (2012) Labelling of nucleosides and oligonucleotides by solvatochromic 4-aminophthalimide fluorophore for studying DNA–protein interactions. Chem Sci 3:2797–2806. doi:10.1039/C2SC20404E

    Article  CAS  Google Scholar 

  105. Gramlich P, Warncke S, Gierlich J, Carell T (2008) Click–click–click: single to triple modification of DNA. Angew Chem Int Ed 47:3442–3444. doi:10.1002/anie.200705664

    Article  CAS  Google Scholar 

  106. Seela F, Sirivolu VR (2008) Pyrrolo-dC oligonucleotides bearing alkynyl side chains with terminal triple bonds: synthesis, base pairing and fluorescent dye conjugates prepared by the azide–alkyne “click” reaction. Org Biomol Chem 6:1674–1687. doi:10.1039/b719459e

    Article  CAS  PubMed  Google Scholar 

  107. Weisbrod SH, Marx A (2007) A nucleoside triphosphate for site-specific labelling of DNA by the Staudinger ligation. Chem Commun 1828–1830. doi:10.1039/b809528k

  108. Baccaro A, Weisbrod SH, Marx A (2007) DNA conjugation by the Staudinger Ligation: new thymidine analogues. Synthesis 1949–1954. doi:10.1055/s-2007-983728

    Google Scholar 

  109. Borsenberger V, Howorka S (2009) Diene-modified nucleotides for the Diels–Alder-mediated functional tagging of DNA. Nucleic Acids Res 37:1477–1485. doi:10.1093/nar/gkn1066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Schoch J, Wiessler M, Jäschke A (2010) Post-synthetic modification of DNA by inverse-electron-demand Diels–Alder reaction. J Am Chem Soc 132:8846–8847. doi:10.1021/ja102871p

    Article  CAS  PubMed  Google Scholar 

  111. Schoch J, Staudt M, Samanta A, Wiessler M, Jäschke A (2012) Site-specific one-pot dual labeling of DNA by orthogonal cycloaddition chemistry. Bioconjugate Chem 23:1382–1385. doi:10.1021/bc300181n

    Article  CAS  Google Scholar 

  112. Raindlová V, Pohl R, Hocek M (2012) Synthesis of aldehyde‐linked nucleotides and DNA and their bioconjugations with lysine and peptides through reductive amination. Chem Eur J 18:4080–4087. doi:10.1002/chem.201103270

    Article  PubMed  CAS  Google Scholar 

  113. Gourlain T, Sidorov A, Mignet N, Thorpe SJ et al (2001) Enhancing the catalytic repertoire of nucleic acids. II. Simultaneous incorporation of amino and imidazolyl functionalities by two modified triphosphates during PCR. Nucleic Acids Res 29:1898–1905. doi:10.1093/nar/29.9.1898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Imaizumi Y, Kasahara Y, Fujita H, Kitadume S et al (2013) Efficacy of base-modification on target binding of small molecule DNA aptamers. J Am Chem Soc 135:9412–9419. doi:10.1021/ja4012222

    Article  CAS  PubMed  Google Scholar 

  115. Macíčková-Cahová H, Hocek M (2009) Cleavage of adenine-modified functionalized DNA by type II restriction endonucleases. Nucleic Acids Res 37:7612–7622. doi:10.1093/nar/gkp845

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Macíčková‐Cahová H, Pohl R, Hocek M (2011) Cleavage of functionalized DNA containing 5‐modified pyrimidines by type II restriction endonucleases. ChemBioChem 12:431–438. doi:10.1002/cbic.201000644

    Article  PubMed  CAS  Google Scholar 

  117. Mačková M, Boháčová S, Perlíková P et al (2015) Polymerase synthesis and restriction enzyme cleavage of DNA containing 7-substituted 7-deazaguanine. ChemBioChem 16:2225–2236. doi:10.1002/cbic.201500315

    Article  PubMed  CAS  Google Scholar 

  118. Vaníková Z, Hocek M (2014) Polymerase synthesis of photocaged DNA resistant against cleavage by restriction endonucleases. Angew Chem Int Ed 53:6734–6737. doi:10.1002/anie.201402370

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gilead Sciences & IOCB Research Center, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 16610, Prague 6, Czech Republic

    Jitka Dadová, Hana Cahová & Michal Hocek

  2. Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 12843, Prague 2, Czech Republic

    Michal Hocek

Authors
  1. Jitka Dadová
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hana Cahová
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michal Hocek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michal Hocek .

Editor information

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

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Dadová, J., Cahová, H., Hocek, M. (2016). Polymerase Synthesis of Base-Modified DNA. 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_6

Download citation

Publish with us

Policies and ethics

Search

Navigation