mRNA and snRNA Cap Analogs: Synthesis and Applications

  • Janusz Stepinski
  • Edward DarzynkiewiczEmail author
Part of the RNA Technologies book series (RNATECHN)


Almost all eukaryotic mRNAs have a monomethylguanosine cap structure consisting of 7-methyl guanosine that is connected via 5′–5′ triphosphate bond to the next nucleoside (m7GpppN; MMG-cap) on their 5′ termini. In unicellular kinetoplastida, including Leishmanias (responsible for a wide spectrum of diseases), the cap is unusually highly methylated (m7Gpppm3 6,6,2′Apm2′Apm2′Cpm2 3,2′U), known as cap-4, while in nematodes (e.g., C. elegans or Ascaris), the mRNA cap is ended with trimethylguanosine (m3 2,2,7GpppN; TMG-cap). A large class of uridine-rich small nuclear RNAs (U snRNAs) on their 5′ termini have also TMG-cap.

Over the last three decades several classes of 5′ mRNA cap analogs, including the natural ones (MMG-cap, TMG-cap, cap-4), have been synthesized in our lab and by other groups. They were serving as valuable tools in elucidating molecular mechanisms of such cap-regulated cellular processes as protein translation initiation, pre-mRNA splicing, RNA intracellular transport, mRNA turnover, and cap-dependent translation inhibition by microRNAs. Some of the synthetic cap dinucleotides (anti-reverse cap analogs; ARCAs), adopted to construct mRNA transcripts with the increased translational efficiency, have found commercial application in production of proteins. In this chapter, we describe the strategies and technical approaches in the synthesis of natural and modified cap analogs. Their application in biology and more recently, in medical studies is also reviewed.


5′ mRNA cap Trimethylguanosine cap cap-4 Capped oligonucleotides Anti-reverse cap analogs Non-hydrolyzable synthetic cap analogs Cap-binding proteins Capping enzymes Decapping enzymes Translation inhibitors Antitumor mRNA vaccines 



This work was supported by grants from the Ministry of Science and Higher Education (Poland) N 301 096 339, National Science Centre (Poland) UMO-2012/07/B/NZ1/00118 and UMO-2013/08/A/NZ1/00866, and National Center of Research and Development (02/EuroNanoMed/2011).


  1. Adam A, Moffat JG (1966) Dismutation reactions of nucloeside polyphosphates. V. Syntheses of P1, P4-di(guanosine-5′) tetraphosphate and P1, P3-di(guanosine-5′) triphosphate. J Am Chem Soc 88:838–842PubMedCrossRefGoogle Scholar
  2. Adams BL, Morgan M, Muthukrishnan S et al (1978) The effect of “cap” analogs on reovirus mRNA binding to wheat germ ribosomes. J Biol Chem 253:2589–2595PubMedGoogle Scholar
  3. Banerjee H, Palenchar JB, Lukaszewicz M et al (2009) Identification of the HIT-45 protein from Trypanosoma brucei as an FHIT protein/dinucleoside triphosphatase: Substrate specificity studies on the recombinant and endogenous proteins. RNA 15:1554–1564PubMedCentralPubMedCrossRefGoogle Scholar
  4. Belanger F, Stepinski J, Darzynkiewicz E et al (2010) Characterization of hMTr1, a human Cap1 2′-O-ribose methyltransferase. J Biol Chem 285:33037–33044PubMedCentralPubMedCrossRefGoogle Scholar
  5. Benarroch D, Jankowska-Anyszka M, Stepinski J et al (2010) Cap analog reveal three clades of cap guanine-N2 methyltransferases with distinct methyl acceptor specificities. RNA 16:211–220PubMedCentralPubMedCrossRefGoogle Scholar
  6. Blackburn GM, Guo M, McLennan AG (1992) Synthetic structural analogues of dinucleoside polyphosphates. In: McLennan AG (ed) Ap4A and other dinuleoside polyphosphates. CRC, Boca Raton, FL, pp 305–342Google Scholar
  7. Blagden SP, Willis AE (2011) The biological and therapeutic relevance of mRNA translation in cancer. Nat Rev Clin Oncol 8:280–291PubMedCrossRefGoogle Scholar
  8. Boland A, Tritschler F, Heimstaedt S et al (2010) Crystal structure and ligand binding of the MID domain of a eukaryotic Argonaute protein. EMBO Rep 11:522–527PubMedCentralPubMedCrossRefGoogle Scholar
  9. Brownlee GG, Fodor E, Pritlove DC et al (1995) Solid phase synthesis of 5′-diphosphorylated oligoribonucleotides and their conversion to capped m7Gppp-oligoribonucleotides for use as primers for influenza A virus RNA polymerase in vitro. Nucleic Acids Res 23:2641–2647PubMedCentralPubMedCrossRefGoogle Scholar
  10. Burgess K, Cook D (2000) Syntheses of nucleoside triphosphates. Chem Rev 100:2047–2059PubMedCrossRefGoogle Scholar
  11. Cai A, Jankowska-Anyszka M, Centers A et al (1999) Quantitative assessment of mRNA cap analogues as inhibitors of in vitro translation. Biochemistry 38:8538–8547PubMedCrossRefGoogle Scholar
  12. Calero G, Wilson K, Ly T et al (2002) Structural basis of m7GpppG binding to the nuclear cap-binding complex. Nat Struct Biol 9:912–917PubMedCrossRefGoogle Scholar
  13. Canaani D, Revel M, Groner Y (1976) Translational discrimination of “capped” and “non-capped” mRNAs: Inhibition by a series of chemical analogs of m7GpppX. FEBS Lett 64:326–331PubMedCrossRefGoogle Scholar
  14. Chavan AJ, Rychlik W, Blaas D et al (1990) Phenyl azide substituted and benzophenone-substituted phosphonamides of 7-methylguanosine 5′-triphosphate as photoaffinity probes for protein-synthesis initiation factor eIF-4E and a proteolytic fragment containing the cap-binding site. Biochemistry 29:5521–5529PubMedCrossRefGoogle Scholar
  15. Chlebicka L, Wieczorek Z, Stolarski R et al (1995) Synthesis and properties of mRNA 5′-cap analogues with 7-methylguanine replaced by benzimidazole or 3-methylbenzimidazole. Nucleosides Nucleotides 14:771–775CrossRefGoogle Scholar
  16. Cho PF, Poulin F, Cho-Park YA et al (2005) A new paradigm for translational control: inhibition via 5′-3′ mRNA tethering by Bicoid and the eIF4E cognate 4EHP. Cell 121:411–423PubMedCrossRefGoogle Scholar
  17. Cohen LS, Mikhli C, Friedman C et al (2004) Nematode m7GpppG – and m3 2,2,7GpppG – RNA decapping: Activities in Ascaris embryos and characterization of C. elegans scavenger DcpS. RNA 10:1609–1624PubMedCentralPubMedCrossRefGoogle Scholar
  18. Contreras R, Cheroutre H, Degrave W et al (1982) Simple, efficient in vitro synthesis of capped RNA useful for direct expression of cloned eukaryotic genes. Nucleic Acids Res 10:6353–6362PubMedCentralPubMedCrossRefGoogle Scholar
  19. Cramer F, Schaller H, Staab HA (1961) Zur Chemie der “Energiereichen Phosphate” XI. Darstellung von Imidazoliden der Phosphorsäure. Chem Ber 94:1612–1621CrossRefGoogle Scholar
  20. Darzynkiewicz E, Antosiewicz J, Ekiel I et al (1981) Methyl esterification of m7Gp reversibly blocks its activity as an analog of eukaryotic mRNA 5′-caps. J Mol Biol 153:451–453PubMedCrossRefGoogle Scholar
  21. Darzynkiewicz E, Ekiel I, Tahara SM et al (1985) Chemical synthesis and characterization of 7-methylguanosine cap analogues. Biochemistry 24:1701–1707CrossRefGoogle Scholar
  22. Darzynkiewicz E, Ekiel I, Lassota P et al (1987) Inhibition of eukaryotic translation by analogues of messenger RNA 5′-cap: chemical and biological consequences of 5′-phosphate modifications of 7-methylguanosine 5′-monophosphate. Biochemistry 26:4372–4380PubMedCrossRefGoogle Scholar
  23. Darzynkiewicz E, Stepinski J, Ekiel I et al (1988) ß-Globin mRNAs capped with m7G, m2 2,7G or m3 2,2,7G differ in intrinsic translation efficiency. Nucleic Acids Res 16:8953–8962PubMedCentralPubMedCrossRefGoogle Scholar
  24. Darzynkiewicz E, Stepinski J, Ekiel I et al (1989) Inhibition of eukaryotic translation by nucleoside 5′-monophosphate analogues of mRNA 5′-cap: Changes in N7 substituent affect analogue activity. Biochemistry 28:4771–4778PubMedCrossRefGoogle Scholar
  25. Darzynkiewicz E, Stepinski J, Tahara SM et al (1990) Synthesis, conformation and hydrolytic stability of P1, P3-dinucleoside triphosphates related to mRNA 5′-cap, and comparative kinetic studies on their nucleoside and nucleoside monophosphate analogs. Nucleosides Nucleotides 9:599–618CrossRefGoogle Scholar
  26. Darzynkiewicz E, Rhoads RE, Stepinski J (2006) Synthesis and use of anti-reverse mRNA cap analogues. US Patent 7,074,596, 11 July 2006Google Scholar
  27. Deshmukh MV, Jones BN, Quang-Dang D-U et al (2008) mRNA decapping is promoted by an RNA binding channel in Dcp2. Mol Cell 29:324–336PubMedCrossRefGoogle Scholar
  28. Djuranovic S, Zinchenko MK, Hur JK et al (2010) Allosteric regulation of Argonaute proteins by miRNAs. Nat Struct Mol Biol 17:144–150PubMedCentralPubMedCrossRefGoogle Scholar
  29. Eckstein F (1970) Nucleoside phosphorothioates. J Am Chem Soc 92:4718–4723PubMedCrossRefGoogle Scholar
  30. Engel R (1977) Phosphonates as analogs of natural phosphates. Chem Rev 77:349–367CrossRefGoogle Scholar
  31. Fabian MR, Sonenberg N, Filipowicz W (2010) Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79:351–379PubMedCrossRefGoogle Scholar
  32. Fischer U, Lührmann R (1990) An essential signaling role for the m3G cap in the transport of U1 snRNP to the nucleus. Science 249:786–790PubMedCrossRefGoogle Scholar
  33. Fischer U, Darzynkiewicz E, Tahara SM et al (1991) Diversity in the signals required for nuclear accumulation of U snRNPs and variety in the pathways of nuclear transport. J Cell Biol 113:705–714PubMedCrossRefGoogle Scholar
  34. Fischer U, Sumpter V, Sekine M et al (1993) Nucleocytoplasmic transport of u snRNPs – definition of a nuclear location signal in the Sm core domain that binds a transport receptor independently of the m3G cap. EMBO J 12:573–583PubMedCentralPubMedGoogle Scholar
  35. Frank F, Fabian MR, Stepinski J et al (2011) Structural analysis of 5′-mRNA-cap interactions with the human AGO2 MID domain. EMBO Rep 12:415–420PubMedCentralPubMedCrossRefGoogle Scholar
  36. Fukuoka K, Suda F, Suzuki R et al (1994a) One-pot reaction for the synthesis of m7G5′pppG and m7G5′pppA by using an activatable bifunctional phoshorylating reagent. Tetrahedron Lett 35:1063–1066CrossRefGoogle Scholar
  37. Fukuoka K, Suda F, Suzuki R et al (1994b) Large scale synthesis of the cap part in messenger RNA using new type of bifunctional phoshorylating reagent. Nucleosides Nucleotides 13:1557–1567CrossRefGoogle Scholar
  38. Furuichi Y, Shatkin AJ (2000) Viral and cellular mRNA capping: Past and prospects. Adv Virus Res 55:135–184PubMedCrossRefGoogle Scholar
  39. Gingras AC, Raught B (1999) eIF4E initiation factors: Effectors of mRNA recruitment to ribosomes and regulators of translation. Annu Rev Biochem 68:913–963PubMedCrossRefGoogle Scholar
  40. Glass RS, Singh WP, Jung W et al (1993) Monoselenophosphate: Synthesis, characterization, and identity with the prokaryotic biological selenium donor, compound SePX. Biochemistry 32:12555–12559PubMedCrossRefGoogle Scholar
  41. Graff JR, Konicek BW, Vincent TM et al (2007) Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity. J Clin Invest 117:2638–2648PubMedCentralPubMedCrossRefGoogle Scholar
  42. Graff JR, Konicek BW, Carter JH et al (2008) Targeting the eukaryotic translation initiation factor 4E for cancer therapy. Cancer Res 68:631–634PubMedCrossRefGoogle Scholar
  43. Grudzien E, Stepinski J, Jankowska-Anyszka M et al (2004) Novel cap analogs for in vitro synthesis of mRNAs with high translational efficiency. RNA 10:1479–1487PubMedCentralPubMedCrossRefGoogle Scholar
  44. Grudzien E, Kalek M, Jemielity J et al (2006) Differential inhibition of mRNA degradation pathways by novel cap analogs. J Biol Chem 281:1857–1867PubMedCrossRefGoogle Scholar
  45. Grudzien-Nogalska E, Stepinski J, Jemielity J et al (2007) Synthesis of anti-reverse cap analogs (ARCAs) and their application in protein translation and stability. Methods Enzymol 431:203–227PubMedCrossRefGoogle Scholar
  46. Grudzien-Nogalska E, Kowalska J, Su W et al (2013) Synthetic mRNAs with superior translation and stability properties. Methods Mol Biol 969:55–72PubMedCrossRefGoogle Scholar
  47. Guranowski A, Wojdyla AM, Zimny J et al (2010a) Recognition of different nucleotidyl-derivatives as substrates of reactions catalyzed by various HIT-proteins. New J Chem 34:888–893CrossRefGoogle Scholar
  48. Guranowski A, Wojdyla AM, Zimny J et al (2010b) Dual activity of certain HIT-proteins: A. thaliana Hint4 and C-elegans DcpS act on adenosine 5′-phosphosulfate as hydrolases (forming AMP) and as phosphorylases (forming ADP). FEBS Lett 584:93–98PubMedCrossRefGoogle Scholar
  49. Hamm J, Mattaj IW (1990) Monomethylated cap structures facilitate RNA export from the nucleus. Cell 63:109–118PubMedCrossRefGoogle Scholar
  50. Hamm J, Darzynkiewicz E, Tahara SM et al (1990) The trimethylguanosine cap structure of U1 snRNA Is a component of a bipartite nuclear targeting signal. Cell 62:569–577PubMedCrossRefGoogle Scholar
  51. Han QW, Gaffney BL, Jones RA (2006) One-flask synthesis of dinucleoside tetra- and pentaphosphates. Org Lett 8:2075–2077PubMedCentralPubMedCrossRefGoogle Scholar
  52. Hata T, Nakagawa I, Shimotohno K et al (1976) The synthesis of α, γ-dinucleoside triphosphates. The confronted nucleotide structure found at the 5′-terminus of eukaryote messenger ribonucleic acid. Chem Lett 1976:987–990CrossRefGoogle Scholar
  53. He KH, Hasan A, Krzyzanowska B et al (1998) Synthesis and separation of diastereomers of ribonucleoside 5′-(α-P-borano)triphosphates. J Org Chem 63:5769–5773PubMedCrossRefGoogle Scholar
  54. Hendler SS, Fürer E, Srinivasan PR (1970) Synthesis and chemical properties of monomers and polymers containing 7-methylguanine and an investigation of their substrate or template properties for bacterial deoxyribonucleic acid or ribonucleic acid polymerases. Biochemistry 9:4141–4153PubMedCrossRefGoogle Scholar
  55. Hickey ED, Weber LA, Baglioni C (1976) Inhibition of initiation of protein synthesis by 7-methylguanosine-5′-monophosphate. Proc Natl Acad Sci U S A 73:19–23PubMedCentralPubMedCrossRefGoogle Scholar
  56. Hickey ED, Weber LA, Baglioni C et al (1977) Relation between inhibition of protein synthesis and conformation of 5′-phosphorylated 7-methylguanosine derivatives. J Mol Biol 109:173–183PubMedCrossRefGoogle Scholar
  57. Hoard DE, Ott DG (1965) Conversion of mono- and oligodeoxyribonucleotides to 5′-triphosphates. J Am Chem Soc 87:1785–1788PubMedCrossRefGoogle Scholar
  58. Hodel AE, Gershon PD, Quiocho FA (1998) Structural basis for sequence-nonspecific recognition of 5′-capped mRNA by a cap-modifying enzyme. Mol Cell 1:443–447PubMedCrossRefGoogle Scholar
  59. Honcharenko M, Romanowska J, Alvira M et al (2012) Capping of oligonucleotides with “clickable” m3G-CAPs. RSC Adv 2:12949–12962CrossRefGoogle Scholar
  60. Honcharenko M, Zytek M, Bestas B et al (2013) Synthesis and evaluation of stability of m3G-CAP analogues in serum-supplemented medium and cytosolic extract. Bioorg Med Chem 21(24):7921–7928, PubMedCrossRefGoogle Scholar
  61. Huber J, Cronshagen U, Kadokura M et al (1998) Snurportin1, an m3G-cap-specific nuclear import receptor with a novel domain structure. EMBO J 17:4114–4126PubMedCentralPubMedCrossRefGoogle Scholar
  62. Imai KI, Fujii S, Takanohashi K et al (1969) Studies on phosphorylation. 4. Selective phosphorylation of primary hydroxyl group in nucleosides. J Org Chem 34:1547–1550CrossRefGoogle Scholar
  63. Inoue K, Ohno M, Sakamoto H et al (1989) Effect of the cap structure on pre-messenger-RNA splicing in Xenopus oocyte nuclei. Genes Dev 3:1472–1479PubMedCrossRefGoogle Scholar
  64. Iwase R, Sekine M, Hata T et al (1988) A new method for the synthesis of capped oligoribonucleotides by use of an appropriately protected 7-methylguanosine diphosphate derivative as a donor for the triphosphate bond formation. Tetrahedron Lett 29:2969–2972CrossRefGoogle Scholar
  65. Iwase R, Sekine M, Tokumoto Y et al (1989) Synthesis of N2, N2,7-trimethylguanosine cap derivatives. Nucleic Acids Res 17:8979–8989PubMedCentralPubMedCrossRefGoogle Scholar
  66. Iwase R, Maeda M, Fujiwara T et al (1992) Molecular design of eukaryotic messenger RNA and its chemical synthesis. Nucleic Acids Res 20:1643–1648PubMedCentralPubMedCrossRefGoogle Scholar
  67. Izaurralde E, Stepinski J, Darzynkiewicz E et al (1992) A cap binding protein that may mediate nuclear export of RNA polymerase II-transcribed RNAs. J Cell Biol 118:1287–1295PubMedCrossRefGoogle Scholar
  68. Izaurralde E, Lewis J, McGuigan C et al (1994) A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell 78:657–668PubMedCrossRefGoogle Scholar
  69. Izaurralde E, Lewis J, Gamberi C et al (1995) A cap-binding protein complex mediating U snRNA export. Nature 376:709–712PubMedCrossRefGoogle Scholar
  70. Jankowska M, Temeriusz A, Stolarski R et al (1993a) Synthesis of m2,7GTP- and m2,2,7GTP-Sepharose 4B: New affinity resins for isolation of cap binding proteins. Collect Czech Chem Commun 58(Special issue):132–137Google Scholar
  71. Jankowska M, Stepinski J, Stolarski R et al (1993b) Synthesis and properties of new NH2 and N7 substituted GMP and GTP 5′-mRNA cap analogues. Collect Czech Chem Commun 58(Special issue):138–141Google Scholar
  72. Jankowska M, Stepinski J, Stolarski R et al (1996) 1H NMR and fluorescence studies of new rnRNA 5′-cap analogues. Collect Czech Chem Commun 61(Special issue):S197–S202Google Scholar
  73. Jankowska-Anyszka M, Piecyk K (2011) Dinucleotide cap analogue affinity resins for purification of proteins that specifically recognize the 5′ end of mRNA. Bioorg Med Chem Lett 21:6131–6134PubMedCrossRefGoogle Scholar
  74. Jankowska-Anyszka M, Lamphear BJ, Aamodt EJ et al (1998) Multiple isoforms of eukaryotic protein synthesis initiation factor 4E in Caenorhabditis elegans can distinguish between mono- and trimethylated mRNA cap structures. J Biol Chem 273:10538–10542PubMedCrossRefGoogle Scholar
  75. Jankowska-Anyszka M, Piecyk K, Samonina-Kosicka J (2011) Synthesis of a new class of ribose functionalized dinucleotide cap analogues for biophysical studies on interaction of cap-binding proteins with the 5′ end of mRNA. Org Biomol Chem 9:5564–5572PubMedCrossRefGoogle Scholar
  76. Jarmolowski A, Boelens WC, Izaurralde E et al (1994) Nuclear export of different classes of RNA is mediated by specific factors. J Cell Biol 124:627–635PubMedCrossRefGoogle Scholar
  77. Jemielity J, Stepinski J, Jaremko M et al (2003a) Synthesis of novel mRNA 5′ cap-analogues: Dinucleoside P1, P3-tri- P1, P4-tetra- and P1, P5-pentaphosphates. Nucleosides Nucleotides Nucleic Acids 22:691–694PubMedCrossRefGoogle Scholar
  78. Jemielity J, Fowler T, Zuberek J et al (2003b) Novel ‘anti-reverse’ cap analogs with superior translational properties. RNA 9:1108–1122PubMedCentralPubMedCrossRefGoogle Scholar
  79. Jemielity J, Pietrowska-Borek M, Starzynska E et al (2005a) Synthesis and enzymatic characterization of methylene analogs of adenosine 5′-tetraphosphate (p4A). Nucleosides Nucleotides Nucleic Acids 24:589–593PubMedCrossRefGoogle Scholar
  80. Jemielity J, Heinonen P, Lönnberg H et al (2005b) A novel approach to solid phase chemical synthesis of oligonucleotide mRNA cap analogs. Nucleosides Nucleotides Nucleic Acids 24:601–605PubMedCrossRefGoogle Scholar
  81. Jemielity J, Kowalska J, Rydzik AM et al (2010) Synthetic mRNA cap analogs with a modified triphosphate bridge – synthesis, applications and prospects. New J Chem 34:829–844CrossRefGoogle Scholar
  82. Jemielity J, Lukaszewicz M, Kowalska J et al (2012a) Synthesis of biotin labelled cap analogue – incorporable into mRNA transcripts and promoting cap-dependent translation. Org Biomol Chem 10:8570–8574PubMedCrossRefGoogle Scholar
  83. Jemielity J, Grudzien-Nogalska E, Kowalska J et al (2012b) Synthesis and use of anti-reverse phosphorothioate analogs of the messenger RNA cap. US Patent 08,153,773, 10 Apr 2012Google Scholar
  84. Jia Y, Chiu T-L, Amin EA et al (2010) Design, synthesis and evaluation of analogs of initiation factor 4E (eIF4E) cap-binding antagonist Bn-7-GMP. Eur J Med Chem 45:1304–1313PubMedCentralPubMedCrossRefGoogle Scholar
  85. Joshi B, Cameron A, Jagus R (2004) Characterization of mammalian eIF4E-family members. Eur J Biochem 271:2189–2203PubMedCrossRefGoogle Scholar
  86. Kadokura M, Wada T, Urashima C et al (1997) Efficient synthesis of γ-methyl-capped guanosine 5′-triphosphate as a 5′-terminal unique structure of U6 RNA via a new triphosphate bond formation involving activation of methyl phosphorimidazolidate using ZnCl2 as a catalyst in DMF under anhydrous conditions. Tetrahedron Lett 38:8359–8362CrossRefGoogle Scholar
  87. Kadokura M, Wada T, Seio K et al (2001) Solid-phase synthesis of 5′-terminal TMG-capped trinucleotide block of U1 snRNA. Tetrahedron Lett 42:8853–8856CrossRefGoogle Scholar
  88. Kalek M, Jemielity J, Grudzien E et al (2005a) Synthesis and biochemical properties of novel mRNA 5′ cap analogs resistant to enzymatic hydrolysis. Nucleosides Nucleotides Nucleic Acids 24:615–621PubMedCrossRefGoogle Scholar
  89. Kalek M, Jemielity J, Stepinski J et al (2005b) A direct method for the synthesis of nucleoside 5′-methylenebis(phosphonate)s from nucleosides. Tetrahedron Lett 46:2417–2421CrossRefGoogle Scholar
  90. Kalek M, Jemielity J, Darzynkiewicz ZM et al (2006) Enzymatically stable 5′ mRNA cap analogs: synthesis and binding studies with human DcpS decapping enzyme. Bioorg Med Chem 14:3223–3230PubMedCrossRefGoogle Scholar
  91. Keiper BD, Lamphear BJ, Deshpande AM et al (2000) Functional characterization of five eIF4E isoforms in Caenorhabditis elegans. J Biol Chem 275:10590–10596PubMedCrossRefGoogle Scholar
  92. Kijewska K, Jarzebinska A, Kowalska J et al (2013) Magnetic-nanoparticle-decorated polypyrrole microvessels: Toward encapsulation of mRNA cap analogues. Biomacromolecules 14:1867–1876PubMedCrossRefGoogle Scholar
  93. Kim J, Chou T-F, Griesgraber GW et al (2004) Direct measurement of nucleoside monophosphate delivery from a phosphoramidate pronucleotide by stable isotope labeling and LC-ESI-MS/MS. Mol Pharm 1:102–111PubMedCrossRefGoogle Scholar
  94. Kiriakidou M, Tan GS, Lamprinaki S et al (2007) An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell 129:1141–1151PubMedCrossRefGoogle Scholar
  95. Kohno K, Nishiyama S, Kamimura T et al (1985) Chemical synthesis of capped RNA fragments and their ability to complex with eukaryotic ribosomes. Nucleic Acids Res Symp Ser 16:233–236Google Scholar
  96. Konarska MM, Padgett RA, Sharp PA (1984) Recognition of cap structure in splicing in vitro of messenger-RNA precursors. Cell 38:731–736PubMedCrossRefGoogle Scholar
  97. Konicek BW, Dumstorf CA, Graff JR (2008) Targeting the eIF4E translation initiation complex for cancer therapy. Cell Cycle 7:2466–2471PubMedCrossRefGoogle Scholar
  98. Kore AR, Charles I (2010a) Synthesis of new dinucleotide mRNA cap analogs containing 2,6-diaminopurine moiety. Lett Org Chem 7:200–202CrossRefGoogle Scholar
  99. Kore AR, Charles I (2010b) Synthesis and evaluation of 2′-O-allyl substituted dinucleotide cap analog for mRNA translation. Bioorg Med Chem 18:8061–8065PubMedCrossRefGoogle Scholar
  100. Kore AR, Shanmugasundaram M (2008) Synthesis and biological evaluation of trimethyl-substituted cap analogs. Bioorg Med Chem Lett 18:880–884PubMedCrossRefGoogle Scholar
  101. Kore AR, Shanmugasundaram M, Charles I et al (2007) Synthesis and application of 2′-fluoro-substituted cap analogs. Bioorg Med Chem Lett 17:5295–5299PubMedCentralPubMedCrossRefGoogle Scholar
  102. Kore AR, Charles I, Shanmugasundaram M et al (2008a) Recent developments in 5′-terminal cap analogs: synthesis and biological ramifications. Mini Rev Org Chem 5:179–192CrossRefGoogle Scholar
  103. Kore AR, Shanmugasundaram M, Vlassov AV (2008b) Synthesis and application of a new 2′,3′-isopropylidene guanosine substituted cap analog. Bioorg Med Chem Lett 18:4828–4832PubMedCrossRefGoogle Scholar
  104. Kore AR, Shanmugasundaram M, Charles I et al (2009) Locked nucleic acid (LNA)-modified dinucleotide mRNA cap analogue: Synthesis, enzymatic incorporation, and utilization. J Am Chem Soc 131:6364–6365PubMedCrossRefGoogle Scholar
  105. Kore AR, Shanmugasundaram M, Barta TJ (2010a) Synthesis and substrate validation of cap analogs containing 7-deazaguanosine moiety by RNA polymerase. Nucleosides Nucleotides Nucleic Acids 29:821–830PubMedCrossRefGoogle Scholar
  106. Kore AR, Charles I, Shanmugasundaram M (2010b) Organic synthesis and improved biological properties of modified mRNA cap analogs. Curr Org Chem 14:1083–1098CrossRefGoogle Scholar
  107. Koukhareva II, Lebedev AV (2004) Chemical route to the capped RNAs. Nucleosides Nucleotides Nucleic Acids 23:1667–1680PubMedCrossRefGoogle Scholar
  108. Kowalska J, Lewdorowicz M, Zuberek J et al (2005) Synthesis and properties of mRNA cap analogs containing phosphorothioate moiety in 5′,5′-triphosphate chain. Nucleosides Nucleotides Nucleic Acids 24:595–600PubMedCrossRefGoogle Scholar
  109. Kowalska J, Lewdorowicz M, Zuberek J et al (2007a) Assignment of the absolute configuration of P-chiral 5′ mRNA cap analogues containing phosphorothioate moiety. Nucleosides Nucleotides Nucleic Acids 26:1301–1305PubMedCrossRefGoogle Scholar
  110. Kowalska J, Lewdorowicz M, Darzynkiewicz E et al (2007b) A simple and rapid synthesis of nucleotide analogues containing a phosphorothioate moiety at the terminal position of the phosphate chain. Tetrahedron Lett 48:5475–5479CrossRefGoogle Scholar
  111. Kowalska J, Zuberek J, Darzynkiewicz ZM et al (2008a) Synthesis and properties of boranophosphate mRNA cap analogues. In: Hocek M (ed) Collection symposium series, vol 10. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of Czech Republic, Prague, pp 383–385Google Scholar
  112. Kowalska J, Lewdorowicz M, Zuberek J et al (2008b) Synthesis and characterization of mRNA cap analogs containing phosphorothioate substitutions that bind tightly to eIF4E and are resistant to the decapping pyrophosphatase DcpS. RNA 14:1119–1131PubMedCentralPubMedCrossRefGoogle Scholar
  113. Kowalska J, Lukaszewicz M, Zuberek J et al (2009) Phosphoroselenoate dinucleotides for modification of mRNA 5′ end. Chembiochem 10:2469–2473PubMedCrossRefGoogle Scholar
  114. Kowalska J, Osowniak A, Zuberek J et al (2012) Synthesis of nucleoside phosphosulfates. Bioorg Med Chem Lett 22:3661–3664PubMedCrossRefGoogle Scholar
  115. Kowalska J, Jemielity J, Darzynkiewicz E et al (2013) mRNA cap analogs. US Patent 08,519,110, 27 Aug 2013Google Scholar
  116. Kuhn AN, Diken M, Kreiter S et al (2010) Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo. Gene Ther 17:961–971PubMedCrossRefGoogle Scholar
  117. Lewdorowicz M, Yoffe Y, Zuberek J et al (2004) Chemical synthesis and binding activity of the trypanosomatid cap-4 structure. RNA 10:1469–1478PubMedCentralPubMedCrossRefGoogle Scholar
  118. Lewdorowicz M, Jemielity J, Kierzek R et al (2007a) Solid-supported synthesis of 5′-mRNA cap-4 from trypanosomatides. Nucleosides Nucleotides Nucleic Acids 26:1329–1333PubMedCrossRefGoogle Scholar
  119. Lewdorowicz M, Stepinski J, Kierzek R et al (2007b) Synthesis of Leishmania cap-4 intermediates, cap-2 and cap-3. Nucleosides Nucleotides Nucleic Acids 26:1339–1348PubMedCrossRefGoogle Scholar
  120. Lewis J, Izaurralde E, Jarmolowski A et al (1996) A nuclear cap-binding complex facilitates association of U1 snRNP with the cap-proximal 5′ splice site. Genes Dev 10:1683–1698PubMedCrossRefGoogle Scholar
  121. Li P, Shaw BR (2004) Convenient synthesis of nucleoside borane diphosphate analogues: Deoxy- and ribonucleoside 5′-Pα-boranodiphosphates. J Org Chem 69:7051–7057PubMedCrossRefGoogle Scholar
  122. Li P, Xu ZH, Liu HY et al (2005) Synthesis of α-P-modified nucleoside diphosphates with ethylenediamine. J Am Chem Soc 127:16782–16783PubMedCrossRefGoogle Scholar
  123. Li S, Jia Y, Jacobson B, McCauley J et al (2013) Treatment of breast and lung cancer cells with a N-7 benzyl guanosine monophosphate tryptamine phosphoramidate pronucleotide (4Ei-1) results in chemosensitization to gemcitabine and induced elF4E proteasomal degradation. Mol Pharm 10:523–531PubMedCrossRefGoogle Scholar
  124. Liu SW, Jiao X, Welch S et al (2008) Analysis of mRNA decapping. Methods Enzymol 448:3–21PubMedCrossRefGoogle Scholar
  125. Liu W, Zhao R, McFarland C et al (2009) Structural insights into parasite eIF4E binding specificity for m7G and m2,2,7G mRNA caps. J Biol Chem 284:31336–31349PubMedCentralPubMedCrossRefGoogle Scholar
  126. Liu W, Jankowska-Anyszka M, Piecyk K et al (2011) Structural basis for nematode eIF4E binding an m2,2,7G-cap and its implications for translation initiation. Nucleic Acids Res 39:8820–8832PubMedCentralPubMedCrossRefGoogle Scholar
  127. Lohrmann R, Orgel LE (1978) Preferential formation of (2′-5′)-linked internucleotide bonds in non-enzymatic reactions. Tetrahedron 34:853–855CrossRefGoogle Scholar
  128. Ludwig J (1981) A new route to nucleoside 5′-triphosphates. Acta Biochim Biophys Hung 16:131–133Google Scholar
  129. 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 54:631–635CrossRefGoogle Scholar
  130. Ma QF, Bathurst IC, Barr PJ et al (1992) New thymidine triphosphate analog inhibitors of human immunodeficiency virus-1 reverse-transcriptase. J Med Chem 35:1938–1941PubMedCrossRefGoogle Scholar
  131. Marcotrigiano J, Gingras AC, Sonenberg N et al (1997) Cocrystal structure of the messenger RNA 5′ cap-binding protein (eIF4E) bound to 7-methyl-GDP. Cell 89:951–961PubMedCrossRefGoogle Scholar
  132. Marshallsay C, Lührmann R (1994) In-vitro nuclear import of snRNPs – cytosolic factors mediate m3G-cap dependence of U1 and U2 snRNP transport. EMBO J 13:222–231PubMedCentralPubMedGoogle Scholar
  133. Mathonnet G, Fabian MR, Svitkin YV et al (2007) MicroRNA function in vitro: inhibition of translational initiation by targeting eIF4F. Science 317:1764–1767PubMedCrossRefGoogle Scholar
  134. Matsuo H, Li H, McGuire AM et al (1997) Structure of translation factor eIF4E bound to m7GDP and interaction with 4E-binding protein. Nat Struct Biol 4:717–724PubMedCrossRefGoogle Scholar
  135. Matsuo H, Moriguchi T, Takagi T et al (2000) Efficient synthesis of 13C,15N-labeled RNA containing the cap structure m7GpppA. J Am Chem Soc 122:2417–2421CrossRefGoogle Scholar
  136. Mattaj IW (1986) Cap trimethylation of U-snRNA is cytoplasmic and dependent on U-snRNP protein-binding. Cell 46:905–911PubMedCrossRefGoogle Scholar
  137. Mazza C, Ohno M, Segref A et al (2001) Crystal structure of the human nuclear cap binding complex. Mol Cell 8:383–396PubMedCrossRefGoogle Scholar
  138. Mazza C, Segref A, Mattaj IW et al (2002) Large-scale induced fit recognition of m7GpppG cap analogue by the human nuclear cap binding complex. EMBO J 21:5548–5557PubMedCentralPubMedCrossRefGoogle Scholar
  139. Mikkola S, Salomaki S, Zhang Z et al (2005) Preparation and properties of mRNA 5′-cap structure. Curr Org Chem 9:999–1022CrossRefGoogle Scholar
  140. Minshall N, Reiter MH, Weil D et al (2007) CPEB interacts with an ovary-specific eIF4E and 4E-T in early Xenopus oocytes. J Biol Chem 282:37389–37401PubMedCrossRefGoogle Scholar
  141. Mittra B, Zamudio JR, Bujnicki JM et al (2008) The TbMTr1 spliced leader RNA cap-1 2′-O-ribose methyltransferase from Trypanosoma brucei acts with substrate specificity. J Biol Chem 283:3161–3172PubMedCrossRefGoogle Scholar
  142. Miyoshi H, Dwyer DS, Keiper BD et al (2002) Discrimination between mono- and trimethylated cap structures by two isoforms of Caenorhabditis elegans eIF4E. EMBO J 21:4680–4690PubMedCentralPubMedCrossRefGoogle Scholar
  143. Moerke NJ, Aktas H, Chen H et al (2007) Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell 128:257–267PubMedCrossRefGoogle Scholar
  144. Moran JR, Whitesides GM (1984) A practical enzymatic-synthesis of (S P)-adenosine 5′-O-(1-thiotriphosphate) ((S P)-ATP-α-S). J Org Chem 49:704–706CrossRefGoogle Scholar
  145. Moreno PMD, Wenska M, Lundin KE et al (2009) A synthetic snRNA m3G-CAP enhances nuclear delivery of exogenous proteins and nucleic acids. Nucleic Acids Res 37:1925–1935PubMedCentralPubMedCrossRefGoogle Scholar
  146. Mukaiyama T, Hashimoto M (1971) Phosphorylation by oxidation-reduction condensation. Preparation of active phosphorylating reagents. Bull Chem Soc Jpn 44:2284CrossRefGoogle Scholar
  147. Murray AW, Atkinson MR (1968) Adenosine 5′-phosphorothioate. A nucleotide analog that is a substrate competitive inhibitor or regulator of some enzymes that interact with adenosine 5′-phosphate. Biochemistry 7:4023–4029PubMedCrossRefGoogle Scholar
  148. Myers TC, Nakamura K, Flesher JW (1963) Phosphonic acid analogs of nucleoside phosphates.1. Synthesis of 5′-adenylyl methylenediphosphonate, a phosphonic acid analog of ATP. J Am Chem Soc 85:3292–3295CrossRefGoogle Scholar
  149. Nakagawa I, Konya S, Ohtani S et al (1980) A “capping” agent: P1-S-phenyl P2-7-methylguanosine-5′ pyrophosphorothioate. Synthesis 1980:556–557CrossRefGoogle Scholar
  150. Natarajan A, Moerke N, Fan YH et al (2004) Synthesis of fluorescein labeled 7-methylguanosinemonophosphate. Bioorg Med Chem Lett 14:2657–2660PubMedCrossRefGoogle Scholar
  151. Niedzwiecka A, Marcotrigiano J, Stepinski J et al (2002) Biophysical studies of eIF4E cap-binding protein: Recognition of mRNA 5′ cap structure and synthetic fragments of eIF4G and 4E-BP1 proteins. J Mol Biol 319:615–635PubMedCrossRefGoogle Scholar
  152. Niedzwiecka A, Stepinski J, Antosiewicz JM et al (2007) Biophysical approach to studies of cap-eIF4E interaction by synthetic cap analogues. Methods Enzymol 430:209–246PubMedCrossRefGoogle Scholar
  153. Ohkubo A, Kondo Y, Suzuki M et al (2013) Chemical synthesis of U1 snRNA derivatives. Org Lett 15:4386–4389PubMedCentralPubMedCrossRefGoogle Scholar
  154. Pasquinelli AE, Dahlberg JE, Lund E (1995) Reverse 5′ caps in RNAs made in vitro by phage RNA polymerases. RNA 1:957–967PubMedCentralPubMedGoogle Scholar
  155. Peng ZH, Sharma V, Singleton SF et al (2002) Synthesis and application of a chain-terminating dinucleotide mRNA cap analog. Org Lett 4:161–164PubMedCrossRefGoogle Scholar
  156. Peyrane F, Selisko B, Decroly E et al (2007) High-yield production of short GpppA- and 7MeGpppA-capped RNAs and HPLC-monitoring of methyltransfer reactions at the guanine-N7 and adenosine-2′O positions. Nucleic Acids Res 35:e26PubMedCentralPubMedCrossRefGoogle Scholar
  157. Piecyk K, Davis RE, Jankowska-Anyszka M (2012) 5′-Terminal chemical capping of spliced leader RNAs. Tetrahedron Lett 53:4843–4847PubMedCentralPubMedCrossRefGoogle Scholar
  158. Ren JH, Goss DJ (1996) Synthesis of a fluorescent 7-methylguanosine analog and a fluorescence spectroscopic study of its reaction with wheatgerm cap binding proteins. Nucleic Acids Res 24:3629–3634PubMedCentralPubMedCrossRefGoogle Scholar
  159. Rupprecht KM, Sonenberg N, Shatkin AJ et al (1981) Design and preparation of affinity columns for the purification of eukaryotic messenger ribonucleic-acid cap binding-protein. Biochemistry 20:6570–6577PubMedCrossRefGoogle Scholar
  160. Ruth JL, Cheng YC (1981) Nucleoside analogs with clinical potential in antivirus chemotherapy – the effect of several thymidine and 2′-deoxycytidine analog 5′-triphosphates on purified human (alpha, beta) and herpes-simplex virus (type-1, type-2) DNA-polymerases. Mol Pharmacol 20:415–422PubMedGoogle Scholar
  161. Rydzik AM, Lukaszewicz M, Zuberek J et al (2009) Synthetic dinucleotide mRNA cap analogs with tetraphosphate 5′,5′ bridge containing methylenebis(phosphonate) modification. Org Biomol Chem 7:4763–4776PubMedCrossRefGoogle Scholar
  162. Rydzik AM, Kulis M, Lukaszewicz M et al (2012) Synthesis and properties of mRNA cap analogs containing imidodiphosphate moiety-fairly mimicking natural cap structure, yet resistant to enzymatic hydrolysis. Bioorg Med Chem 20:1699–1710PubMedCrossRefGoogle Scholar
  163. Sasavage NL, Friderici K, Rottman FM (1979) Specific-inhibition of capped messenger-RNA translation in vitro by m7G5′pppp5′G and m7G5′pppp5′-m7G. Nucleic Acids Res 6:3613–3624PubMedCentralPubMedCrossRefGoogle Scholar
  164. Sawai H, Wakai H, Shimazu M (1991) Facile synthesis of cap portion of messenger RNA by Mn(II) ion catalyzed pyrophosphate formation in aqueous solution. Tetrahedron Lett 32:6905–6906CrossRefGoogle Scholar
  165. Sawai H, Shimazu M, Wakai H et al (1992) Divalent metal ion-catalyzed pyrophosphate bond formation in aqueous solution. Synthesis of nucleotides containing polyphosphate. Nucleosides Nucleotides 11:773–785CrossRefGoogle Scholar
  166. Sawai H, Wakai H, Nakamura-Ozaki A (1999) Synthesis and reactions of nucleoside 5′-diphosphate imidazolide. A nonenzymatic capping agent for 5′-monophosphorylated oligoribonucleotides in aqueous solution. J Org Chem 64:5836–5840CrossRefGoogle Scholar
  167. Sekine M, Nishiyama S, Kamimura T et al (1985) Chemical synthesis of capped oligoribonucleotides, m7G5′pppAUG and m7g5′pppAUGACC. Bull Chem Soc Jpn 58:850–860CrossRefGoogle Scholar
  168. Sekine M, Iwase R, Hata T et al (1989) Synthesis of capped oligoribonucleotides by use of protected 7-methylguanosine 5′-diphosphate derivatives. J Chem Soc Perkin Trans I 1989:969–978CrossRefGoogle Scholar
  169. Sekine M, Kadokura M, Satoh T et al (1996) Chemical synthesis of a 5′-terminal TMG-capped triribonucleotide m3 2,2,7G5′pppAmpUmpA of U1 RNA. J Org Chem 61:4412–4422PubMedCrossRefGoogle Scholar
  170. Setondji J, Remy P, Dirheime G et al (1970) Analogues of nucleoside polyphosphates. 4. synthesis of adenosine 5′-hypophosphate – a structural analogue of ADP. Biochim Biophys Acta 224:136–143PubMedCrossRefGoogle Scholar
  171. Shimazu M, Shinozuka K, Sawai H (1990) Facile synthesis of nucleotides containing polyphosphates by Mn(II) and Cd(II) ion-catalyzed pyrophosphate bond formation in aqueous solution. Tetrahedron Lett 31:235–238CrossRefGoogle Scholar
  172. Smietanski M, Werner M, Purta E et al (2014) Structural analysis of human 2′–O-ribose methyltransferases involved in mRNA cap structure formation. Nat Commun 5:3004. doi: 10.1038/ncomms4004 PubMedCentralPubMedCrossRefGoogle Scholar
  173. Sonenberg N, Hinnebusch AG (2009) Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136:731–745PubMedCentralPubMedCrossRefGoogle Scholar
  174. Sonenberg N, Rupprecht KM, Hecht SM et al (1979) Eukaryotic messenger-RNA cap binding-protein – purification by affinity chromatography on Sepharose-coupled m7GDP. Proc Natl Acad Sci USA 76:4345–4349PubMedCentralPubMedCrossRefGoogle Scholar
  175. Song M-G, Bail S, Kiledjian M (2013) Multiple Nudix family proteins possess mRNA decapping activity. RNA 19:390–399PubMedCentralPubMedCrossRefGoogle Scholar
  176. Sood A, Shaw BR, Spielvogel BF (1990) Boron-containing nucleic-acids. 2. Synthesis of oligodeoxynucleoside boranophosphates. J Am Chem Soc 112:9000–9001CrossRefGoogle Scholar
  177. Stachelska A, Wieczorek Z, Ruszczynska K et al (2002) Interaction of three Caenorhabditis elegans isoforms of translation initiation factor eIF4E with mono- and trimethylated mRNA 5′ cap analogues. Acta Biochim Pol 49:671–682PubMedGoogle Scholar
  178. Stepinski J, Grabowska L, Darzynkiewicz E et al (1990) Synthesis, conformation and hydrolytic stability of modified mRNA 5′-cap structures: P1,P3-dinucleoside triphosphates derived from guanosine and acyclic analogues of 7-methyl-, N2,7-dimethyl- and N2,N2,7-trimethylguanosines. Collect Czech Chem Commun 55(Special Issue):117–120Google Scholar
  179. Stepinski J, Bretner M, Jankowska M et al (1995) Synthesis and properties of P1, P2-, P1, P3- and P1, P4-dinucleoside di-, tri- and tetraphosphate mRNA 5′-cap analogues. Nucleosides Nucleotides 14:717–721Google Scholar
  180. Stepinski J, Waddell C, Stolarski R et al (2001) Synthesis and properties of mRNAs containing the novel “anti-reverse” cap analogues 7-methyl-(3′-O-methyl)GpppG and 7-methyl-(3′-deoxy)GpppG. RNA 7:1486–1495PubMedCentralPubMedGoogle Scholar
  181. Stepinski J, Jemielity J, Lewdorowicz M et al (2002) Catalytic efficiency of divalent metal salts in dinucleoside 5′,5′-triphosphate bond formation. In: Točik Z, Hocek M (eds) Collection symposium series, vol 5. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of Czech Republic, Prague, pp 154–158Google Scholar
  182. Stepinski J, Zuberek J, Jemielity J et al (2005) Novel dinucleoside 5′,5′-triphosphate cap analogues. Synthesis and affinity for murine translation factor eiF4E. Nucleosides Nucleotides Nucleic Acids 24:629–633PubMedCrossRefGoogle Scholar
  183. Stepinski J, Wojcik J, Sienkiewicz A et al (2007) Synthesis and NMR spectral properties of spin labelled mRNA 5′ cap analogue, a new tool for biochemical studies of cap binding proteins. J Phys Condens Matter 19:285202 (10 pp)CrossRefGoogle Scholar
  184. Stock JA (1979) Synthesis of phosphonate analogs of thymidine diphosphate and triphosphate from 5′-O-toluenesulfonylthymidine. J Org Chem 44:3997–4000CrossRefGoogle Scholar
  185. Strasser A, Dickmanns A, Lührmann R et al (2005) Structural basis for m3G-cap-mediated nuclear import of spliceosomal UsnRNPs by snurportin1. EMBO J 24:2235–2243PubMedCentralPubMedCrossRefGoogle Scholar
  186. Strenkowska M, Kowalska J, Lukaszewicz M et al (2010) Towards mRNA with superior translational activity: synthesis and properties of ARCA tetraphosphates with single phosphorothioate modifications. New J Chem 34:993–1007PubMedCentralPubMedCrossRefGoogle Scholar
  187. Strenkowska M, Wanat P, Ziemniak M et al (2012) Preparation of synthetically challenging nucleotides using cyanoethyl P-imidazolides and microwaves. Org Lett 14:4782–4785PubMedCrossRefGoogle Scholar
  188. Su W, Slepenkov S, Grudzien-Nogalska E et al (2011) Translation, stability, and resistance to decapping of mRNAs containing caps substituted in the triphosphate chain with BH3, Se, and NH. RNA 17:978–988PubMedCentralPubMedCrossRefGoogle Scholar
  189. Szczepaniak SA, Jemielity J, Zuberek J et al (2008) Bisphosphonate mRNA cap analog attached to Sepharose for affinity chromatography of decapping enzymes. Nucleic Acids Symp Ser 52:295–296CrossRefGoogle Scholar
  190. Szczepaniak SA, Zuberek J, Darzynkiewicz E et al (2012) Affinity resins containing enzymatically resistant mRNA cap analogs – a new tool for the analysis of cap-binding proteins. RNA 18:1421–1432PubMedCentralPubMedCrossRefGoogle Scholar
  191. Thillier Y, Decroly E, Morvan F et al (2012) Synthesis of 5′ cap-0 and cap-1 RNAs using solid-phase chemistry coupled with enzymatic methylation by human (guanine-N 7)-methyl transferase. RNA 18:856–868PubMedCentralPubMedCrossRefGoogle Scholar
  192. Tomasz J, Vaghefi MM, Ratsep PC et al (1988) Nucleoside imidodiphosphates synthesis and biological-activities. Nucleic Acids Res 16:8645–8664PubMedCentralPubMedCrossRefGoogle Scholar
  193. Topisirovic I, Svitkin YV, Sonenberg N et al (2011) Cap and cap-binding proteins in the control of gene expression. Wiley Interdiscip Rev RNA 2:277–298PubMedCrossRefGoogle Scholar
  194. Townsend LB, Robins RK (1963) Ring cleavage of purine nucleosides to yield possible biogenic precursors of pteridines and riboflavin. J Am Chem Soc 85:242–243CrossRefGoogle Scholar
  195. von der Haar T, Gross JD, Wagner G et al (2004) The mRNA cap-binding protein eIF4E in post-transcriptional gene. Nat Struct Mol Biol 11:503–511PubMedCrossRefGoogle Scholar
  196. Warminski M, Kowalska J, Buck J et al (2013) The synthesis of isopropylidene mRNA cap analogs modified with phosphorothioate moiety and their evaluation as promoters of mRNA translation. Bioorg Med Chem Lett 23:3753–3758PubMedCrossRefGoogle Scholar
  197. Webb NR, Chari RVJ, DePillis G et al (1984) Purification of the messenger RNA cap-binding protein using a new affinity medium. Biochemistry 23:177–181PubMedCrossRefGoogle Scholar
  198. Weber LA, Feman ER, Hickey ED et al (1976) Inhibition of HeLa cell messenger RNA translation by 7-methylguanosine 5′-monophosphate. J Biol Chem 251:5657–5662PubMedGoogle Scholar
  199. Westman B, Beeren L, Grudzien E et al (2005) The antiviral drug ribavirin does not mimic the 7-methylguanosine moiety of the mRNA cap structure in vitro. RNA 11:1505–1513PubMedCentralPubMedCrossRefGoogle Scholar
  200. Worch R, Stepinski J, Niedzwiecka A et al (2005a) Novel way of capping mRNA trimer and studies of its interaction with human nuclear cap-binding complex. Nucleosides Nucleotides Nucleic Acids 24:1131–1134PubMedCrossRefGoogle Scholar
  201. Worch R, Niedzwiecka A, Stepinski J et al (2005b) Specificity of recognition of mRNA cap by human nuclear cap-binding complex. RNA 11:1355–1363PubMedCentralPubMedCrossRefGoogle Scholar
  202. Wypijewska del Nogal A, Surleac MD, Kowalska J et al (2013) Analysis of decapping scavenger cap complex using cap analogs reveals molecular determinants for efficient cap binding. FEBS J 280(24):6508–6527. doi: 10.1111/febs.12553 PubMedCrossRefGoogle Scholar
  203. Wypijewska A, Bojarska E, Stepinski J et al (2010) Structural requirements for Caenorhabditis elegans DcpS substrates based on fluorescence and HPLC enzyme kinetic studies. FEBS J 277:3003–3013PubMedCentralPubMedCrossRefGoogle Scholar
  204. Wypijewska A, Bojarska E, Lukaszewicz M et al (2012) 7-Methylguanosine diphosphate (m7GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity. Biochemistry 51:8003–8013PubMedCentralPubMedCrossRefGoogle Scholar
  205. Yamaguchi K, Nakagawa I, Sekine M et al (1984) Chemical synthesis of the 5′-terminal part bearing cap structure of messenger RNA of cytoplasmic polyhedrosis virus (CPV): m7G5′pppAmpG and m7G5′pppAmpGpU. Nucleic Acids Res 12:2939–2954PubMedCentralPubMedCrossRefGoogle Scholar
  206. Yisraeli JK, Melton DA (1989) Synthesis of long, capped transcripts in vitro by SP6 and T7 RNA-polymerases. Methods Enzymol 180:42–50PubMedCrossRefGoogle Scholar
  207. Yoffe Y, Zuberek J, Lewdorowicz M et al (2004) Cap-binding activity of an eIF4E homolog from Leishmania. RNA 10:1764–1775PubMedCentralPubMedCrossRefGoogle Scholar
  208. Yoffe Y, Zuberek J, Lerer A et al (2006) Binding specificities and potential roles of isoforms of eukaryotic initiation factor 4E in Leishmania. Eukaryot Cell 5:1969–1979PubMedCentralPubMedCrossRefGoogle Scholar
  209. Yoffe Y, Léger M, Zinoviev A et al (2009) Evolutionary changes in the Leishmania eIF4F complex involve variations in the eIF4E-eIF4G interactions. Nucleic Acids Res 37:3243–3253PubMedCentralPubMedCrossRefGoogle Scholar
  210. Yoshikawa M, Kato T, Takenishi T (1967) A novel method for phosphorylation of nucleosides to 5′-nucleotides. Tetrahedron Lett 8:5065–5068CrossRefGoogle Scholar
  211. Yount RG, Babcock D, Ballanty W et al (1971) Adenylyl imidodiphosphate, an adenosine triphosphate analog containing a P-N-P linkage. Biochemistry 10:2484–2489PubMedCrossRefGoogle Scholar
  212. Zdanowicz A, Thermann R, Kowalska J et al (2009) Drosophila miR2 Primarily Targets the m7GpppN Cap Structure for Translational Repression. Mol Cell 35:881–888PubMedCrossRefGoogle Scholar
  213. Ziemniak M, Strenkowska M, Kowalska J et al (2013a) Potential therapeutic applications of RNA cap analogs. Future Med Chem 5:1141–1172PubMedCrossRefGoogle Scholar
  214. Ziemniak M, Szabelski M, Lukaszewicz M et al (2013b) Evaluation of fluorescent cap analogues for mRNA labeling. RSC Adv 3:20943–20958CrossRefGoogle Scholar
  215. Zuberek J, Stepinski J, Niedzwiecka A et al (2002) Synthesis of tetraribonucleotide cap analogue m7GpppAm2′pUm2′pAm2′ and its interaction with eukaryotic initiation factor eIF4E. In: Točik Z, Hocek M (eds) Collection symposium series, vol 5. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of Czech Republic, Prague, pp 399–403Google Scholar
  216. Zuberek J, Wyslouch-Cieszynska A, Niedzwiecka A et al (2003) Phosphorylation of eIF4E attenuates its interaction with mRNA 5′ cap analogs by electrostatic repulsion: Intein-mediated protein ligation strategy to obtain phosphorylated protein. RNA 9:52–61PubMedCentralPubMedCrossRefGoogle Scholar
  217. Zuberek J, Jemielity J, Jablonowska A et al (2004) Influence of electric charge variation at residues 209 and 159 on interaction of eIF4E with the mRNA 5′ terminus. Biochemistry 43:5370–5379PubMedCrossRefGoogle Scholar
  218. Zuberek J, Kubacka D, Jablonowska A et al (2007) Weak binding affinity of human 4EHP for mRNA cap analogs. RNA 13:691–697PubMedCentralPubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of Biophysics, Institute of Experimental Physics, Faculty of PhysicsUniversity of WarsawWarsawPoland
  2. 2.Centre of New TechnologiesUniversity of WarsawWarsawPoland

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