Nucleobase Protection of Deoxyribo‐ and Ribonucleosides

Geeta Meher1, Nabin K. Meher2, Radhakrishnan P. Iyer1

1 Spring Bank Pharmaceuticals, Inc., Milford, Massachusetts, 2 PharmAgra Labs, Inc., Brevard, North Carolina
Publication Name:  Current Protocols in Nucleic Acid Chemistry
Unit Number:  Unit 2.1
DOI:  10.1002/cpnc.32
Online Posting Date:  June, 2017
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Oligonucleotides carrying a variety of chemical modifications including conjugates are finding increasing applications in therapeutics, diagnostics, functional genomics, proteomics, and as research tools in chemical and molecular biology. The successful synthesis of oligonucleotides primarily depends on the use of appropriately protected nucleoside building blocks including the exocyclic amino groups of the nucleobases, the hydroxyl groups at the 2′‐, 3′‐, and 5′‐positions of the sugar moieties, and the internucleotide phospho‐linkage. This unit is a thoroughly revised update of the previously published version and describes the recent development of various protecting groups that facilitate reliable oligonucleotide synthesis. In addition, various protecting groups for the imide/lactam function of thymine/uracil and guanine, respectively, are described to prevent irreversible nucleobase modifications that may occur in the presence of reagents used in oligonucleotide synthesis. © 2017 by John Wiley & Sons, Inc.

Keywords: carbamates; cyanoethylation; depurination; nucleobases; N‐acylation; photolytic cleavage; silyl protection

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Table of Contents

  • Salient Features of Oligonucleotide Synthesis
  • General Aspects of Nucleobase Protection
  • Nucleoside Tautomerism and PKA Values
  • Reactivity of Nucleosides
  • Protection of Imide and Lactam Functions
  • Protection of Exocyclic Amino Groups
  • The Problem of Cyano‐Ethylation
  • Protection of Purine Nucleobases: The Problem of Depurination
  • Other Developments in Nucleobase Protection
  • Conclusion
  • Acknowledgments
  • Literature Cited
  • Figures
  • Tables
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Literature Cited

Literature Cited
  Alvarez, K., Vasseur, J.‐J., Beltran, T., & Imbach, J.‐L. (1999). Photocleavable protecting groups as nucleobase protections allowed the solid‐phase synthesis of base‐sensitive SATE‐prooligonucleotides. The Journal of Organic Chemistry, 64, 6319–6328. doi: 10.1021/jo990479h.
  Andrus, A., & Beaucage, S. L. (1988). 2‐Mercaptobenzothiazole—an improved reagent for the removal of methylphosphate protecting groups from oligodeoxynucleotide phosphotriesters. Tetrahedron Letters, 29, 5479–5482. doi: 10.1016/S0040‐4039(00)80791‐1.
  Azzena, U., Dettori, G., Pisano, L., & Pittalis, M. (2007). Microwave‐assisted carbamoylation of Amines. Synthetic Communications, 37, 3623–3634. doi: 10.1080/00397910701557663.
  Balgobin, N., Josephson, S., & Chattopadhyaya, J. B. (1981). A general approach to the chemical synthesis of oligodeoxyribonucleotides. Acta Chemica Scandinavica, B35, 201–212. doi: 10.3891/acta.chem.scand.35b‐0201.
  Barton, D. H. R., Chow, Y. L., Cox, A., & Kirby, G. W. (1962). Photosensitive protection of functional groups. Tetrahedron Letters, 23, 1055–1057. doi: 10.1016/S0040‐4039(00)70957‐9.
  Beaucage, S. L., & Caruthers, M. H. (1981). Deoxynucleoside phosphoramidites—A new class of key intermediates for deoxypolynucleotide synthesis. Tetrahedron Letters, 22, 1859–1862. doi: 10.1016/S0040‐4039(01)90461‐7.
  Beaucage, S. L., & Iyer, R. P. (1992). Advances in the synthesis of oligonucleotides by the phosphoramidite approach. Tetrahedron, 48, 2223–2311. doi: 10.1016/S0040‐4020(01)88752‐4.
  Beaucage, S. L., & Iyer, R. P. (1993a). The functionalization of oligonucleotides via phosphoramidite derivatives. Tetrahedron, 49, 1925–1963. doi: 10.1016/S0040‐4020(01)86295‐5.
  Beaucage, S. L., & Iyer, R. P. (1993b). The synthesis of modified oligonucleotides by the phosphoramidite approach and their applications. Tetrahedron, 49, 6123–6194. doi: 10.1016/S0040‐4020(01)87958‐8.
  Beaucage, S. L., & Iyer, R. P. (1993c). The synthesis of specific ribonucleotides and unrelated phosphorylated biomolecules by the phosphoramidite method. Tetrahedron, 49, 10441–10488. doi: 10.1016/S0040‐4020(01)81543‐X.
  Beier, M., & Pfleiderer, W. (1997). Phthaloyl Strategy: A new approach towards oligodeoxyrobonucleosides. Nucleosides & Nucleotides, 16, 1621–1628. doi: 10.1080/07328319708006240.
  Beier, M., & Pfleiderer, W. (1999). Phthaloyl strategy: A new concept of oligonucleotide synthesis. Helvetica Chimica Acta, 82, 633–644. doi: 10.1002/(SICI)1522‐2675(19990407)82:4<633::AID‐HLCA633>3.0.CO;2‐U.
  Benseler, F., & McLaughlin, L. W. (1986). An improved procedure for the protection of 2′‐deoxyguanosine. Synthesis, 1, 45–46. doi: 10.1055/s‐1986‐31471.
  Bhat, B. (1998). Acylation of nucleosides with N‐acyltetrazole. USPT: US5767270A.
  Bhat, B., & Sanghvi, Y. S. (1997). A mild and highly selective N‐benzoylation of cytosine and adenine bases in nucleosides with N‐benzoyltetrazole. Tetrahedron Letters, 38, 8811–8814. doi: 10.1016/S0040‐4039(97)10423‐3.
  Bhat, V., Ugarkar, B. G., Sayeed, V. A., Grimm, K., Kosora, N., & Domenico, P. (1989). A simple and convenient method for the selective N‐acylations of cytosine nucleosides. Nucleosides & Nucleotides, 8, 179–183. doi: 10.1080/07328318908054166.
  Boal, J. H., Wilk, A., Harindranath, N., Max, E. E., Kempe, T., & Beaucage, S. L. (1996). Cleavage of oligodeoxyribonucleotides from controlled pore glass supports and their rapid deprotection by gaseous amines. Nucleic Acids Research, 24, 3115–3117. doi: 10.1093/nar/24.15.3115.
  Bridson, P. K., Markiewicz, W., & Reese, C. B. (1977). Acylation of 2′,3′,5′‐tri‐O‐acetylguanosine. Journal of the Chemical Society Chemical Communications, 791–792. doi: 10.1039/C39770000791.
  Brown, J. M., Christodoulou, C., Modak, A. S., Reese, C. B., & Serafinowska, H. T. (1989). Synthesis of the 3′‐terminal half of yeast alanine transfer ribonucleic acid (tRNAala) by the phosphotriester approach in solution. Part 2. Journal of the Chemical Society, Perkin Transactions, 1, 1751–1767. doi: 10.1039/P19890001735.
  Büchi, H., & Khorana, H. G. (1972). CIV. Total synthesis of the structural gene for an alanine transfer ribonucleic acid from yeast. Chemical synthesis of an icosadeoxyribonucleotide corresponding to the nucleotide sequence 31 to 50. Journal of Molecular Biology, 72, 251–288. doi: 10.1016/0022‐2836(72)90148‐9.
  Caruthers, M. H., McBride, L. J., Bracco, L. P., & Dubendorff, J. W. (1985). Studies on nucleotide chemistry 15. Synthesis of oligodeoxynucleotides using amidine protected nucleosides. Nucleosides & Nucleotides, 4, 95–105. doi: 10.1080/07328318508077833.
  Caruthers, M. H., & Roy, S. (2015). Exocyclic nitrogen atom protected nucleoside and method for producing and using the same. USPT: 20150225442 A1 and WO2014022839 A1.
  Chaix, C., Molko, D., & Téoule, R. (1989). The use of labile base protecting groups in oligoribonucleotide synthesis. Tetrahedron Letters, 30, 71–74. doi: 10.1016/S0040‐4039(01)80326‐9.
  Chen, T., Fu, J., & Greenberg, M. M. (2000). Synthesis and deprotection of oligonucleotide under aprotic conditions. Organic Letters, 23, 3691–3694. doi: 10.1021/ol006604p.
  Cho, J. H., Amblard, F., Coats, S. J., & Schinazi, R. F. (2011). Efficient synthesis of nucleoside aryloxy phosphoramidate prodrugs utilizing benzyloxycarbonyl protection. Tetrahedron Letters, 67, 5487–5493. doi: 10.1016/j.tet.2011.05.046.
  Cho, J. H., Coats, S. J., & Schinazi, R. F. (2012). Efficient synthesis of exo‐N‐carbamoyl nucleosides: Application to the synthesis of phosphoramidate prodrugs. Organic Letters, 14, 2488–2491. doi: 10.1021/ol300777p.
  Cieslak, J., & Beaucage, S. L. (2003). Thermolytic properties of 3‐(2‐pyridyl)‐1‐propyl and 2‐[N‐methyl‐N‐(2‐pyridyl)]aminoethyl phosphate/thiophosphate protecting groups in solid‐phase synthesis of oligodeoxyribonucleotides. The Journal of Organic Chemistry, 68, 10123–10129. doi: 10.1021/jo0354490.
  Cieslak, J., Grajkowski, A., Livengood, V., & Beaucage, S. L. (2004). Thermolytic 4‐methylthio‐1‐butyl group for phosphate/thiophosphate protection in solid‐phase synthesis of DNA oligonucleotides. The Journal of Organic Chemistry, 69, 2509–2515. doi: 10.1021/jo035861f.
  Clauwaert, J., & Stockx, J. (1986). Interactions of polynucleotides and their components. I. Dissociation constants of the bases and their derivatives. Zeitschrift fur Naturforschung. Teil B: Chemie Biochemie Biophysik Biologie, 23, 25–30. doi: 10.1515/znb‐1968‐0105.
  den Hartog, J. A. J., Willie, G., Scheublin, R. A., & van Boom, J. H. (1982). Chemical synthesis of a messenger ribonucleic acid fragment: AUGUUCUUCUUCUUCUUC. Biochemistry, 21, 1009–1018. doi: 10.1021/bi00534a028.
  Dikshit, A., Chaddha, M., Singh, R. K., & Misra, K. (1988). Naphthaloyl group: A new selective amino protecting group for deoxynucleosides in oligonucleotide synthesis. Canadian Journal of Chemistry, 66, 2989–2994. doi: 10.1139/v88‐464.
  Dineva, M. A., Galunsky, B., Kasche, V., & Petkov, D. D. (1993). Phenylacetyl group as enzyme clevable aminoprotection of purine nucleoside. Bioorganic & Medicinal Chemistry Letters, 3, 2781–2784. doi: 10.1016/S0960‐894X(01)80763‐0.
  Divakar, K. J., & Reese, C. B. (1982). 4‐(1,2,4‐Triazol‐1‐yl)‐ and 4‐(3‐nitro‐1,2,4‐triazol‐1‐yl)‐1‐(β‐D‐2,3,5‐tri‐O‐acetylarabinofuranosyl)pyr imidin‐2(1H)‐ones. Valuable intermediates in the synthesis of derivatives of 1‐(β‐D‐arabinofuranosyl)cytosine (Ara‐C). Journal of the Chemical Society Perkin Transactions, 1, 1171–1176. doi: 10.1039/P19820001171.
  Dreef‐Tromp, C. M., Hoggerhout, P., van der Marel, G. A., & van Boom, J. H. (1990). A new protected acyl protecting group for exocylic amino functions of nucleobases. Tetrahedron Letters, 31, 427–430. doi: org/10.1016/S0040‐4039(00)94573‐8.
  Dreef‐Tromp, C. M., van Dam, E. M. A., van den Elst, H., van der Marel, G. A., & van Boom, J. H. (1990). Solid‐phase synthesis of H‐Phe‐Tyr‐(pATAT)‐NH2: A nucleopeptide fragment from the nucleorotein of bacteriophage ϕX174. Nucleic Acids Research, 18, 6491–6495. doi: 10.1093/nar/18.22.6491.
  D'Onofrio, J., Napoli, L. D., Fabio, G. D., & Montesarchio, D. (2006). 2‐(Phenylthio)ethyl as a two‐stage base protecting group for thymidine analogues. Synlett, 6, 845–848. doi: 10.1055/s‐2006‐933147.
  Dunn, D. B., & Hall, R. H. (1975). Purines, pyrimidines, nucleosides and nucleotides: Physical constants and spctral properties. In G. D. Fasman (Ed), Handbook of Biochemistry and Molecular Biology (3rd ed., Vol. 1, Nucleic Acids, pp. 65‐125). Boca Raton, Fla: CRC Press.
  Engels, J. W., & Mag, M. (1982). Amide protection in oligodeoxynucleotide synthesis. Nucleosides & Nucleotides, 6, 473–475. doi: 10.1080/07328318708056261.
  Engels, J., & Reidys, R. (1978). Synthesis and application of the photolabile guanosine 3,5‐phosphoric‐o‐nitrobenzylester. Cellular and Molecular Life Sciences, 1, 14–15. doi: 10.1007/BF01921871.
  Engels, J., & Schlaeger, E. J. (1977). Synthesis, structure, and reactivity of adenosine cyclic 3,5‐phosphate benzyl triesters. Journal of Medicinal Chemistry, 20, 907–911. doi: 10.1021/jm00217a008.
  Ferreira, F., & Morvan, F. (2005). Silyl protecting groups for oligonucleotide synthesis removed by a ZnBr2 treatment. Nucleosides & Nucleotides Nucleic Acids, 24, 1009–1013. doi: 10.1081/NCN‐200060342.
  Ferreira, F., Vasseur, J.‐J., & Morvan, F. (2004). Lewis acid deprotection of silyl protected oligonucleotides and base sensitive oligonucleotide analogues. Tetrahedron Letters, 45, 6287–6290. doi: 10.1016/j.tetlet.2004.06.081.
  Francois, P., Hamoir, G., Sonveaux, E., Vermeersch, H., & Ma, Y. (1985). On the phosphorylation of deoxyribonucleosides and the protection of deoxyguanosine. Bulletin des Sociétés Chimiques Belges, 94, 821–823. doi: 10.1002/bscb.19850941109.
  Fourrey, J.‐L., & Varenne, J. (1985). Preparation and phosphorylation reactivity of N‐nonacylated nucleoside phosphoramidites. Tetrahedron Letters, 26, 2663–2666. doi: 10.1016/S0040‐4039(00)98130‐9.
  Froehler, B. C., & Matteucci, M. D. 1983. Dialkylformamidines: Depurination resistant N6‐protecting group or deoxyadenosine. Nucleic Acids Research, 11, 8031–8036. doi: 10.1093/nar/11.22.8031.
  Froehler, B. C., Ng, P. G., & Matteucci, M. D. (1986). Synthesis of DNA via deoxynucleoside H‐phosponate intermediates. Nucleic Acids Research, 14, 5399–5407. doi: 10.1093/nar/14.13.5399.
  Fujii, M., Yamakage, S., Takaku, H., & Hata, T. (1987). (Butylthio)carbonyl group: A new protecting group for the guanine residue in oligoribonucleotide synthesis. Tetrahedron Letters, 28, 5713–5716. doi: 10.1016/S0040‐4039(00)96821‐7.
  Furuta, T., Watanabe, T., Tanabe, S., Sakyo, J., & Matsuba, C. (2007). Phototriggers for nucleobases with improved photochemical properties. Organic Letters, 23, 4717–4720. doi: 10.1021/ol702106t.
  Gaffney, B. L., & Jones, R. A. (1982). A new strategy for the protection of deoxyguanosine during oligonucleotide synthesis. Tetrahedron Letters, 23, 2257–2260. doi: 10.1016/S0040‐4039(00)87315‐3.
  Garegg, P. J., Lindh, I., Regberg, T., Stawinski, J., Str Ömberg, R., & Henrichson, C. (1986). Nucleoside H‐phosphonates. IV. Automated solid phase synthesis of oligoribonucleotides by the hydrogenphosphonate approach. Tetrahedron Letters, 27, 4055–4058. doi: 10.1016/S0040‐4039(00)84909‐6.
  Gilham, P. T., & Khorana, H. G. (1958). Studies on polynucleotides. I. A new and general method for the chemical synthesis of the C5′‐C3′ internucleotidic linkage. Syntheses of deoxyribo‐dinucleotides. Journal of the American Chemical Society, 80, 6212–6222. doi: 10.1021/ja01556a016.
  Givens, R. S., Rubinab, M., & Wirz, J. (2012). Applications of p‐hydroxyphenacyl (pHP) and coumarin‐4‐ylmethyl photoremovable protecting groups. Photochemical & Photobiological Sciences, 11, 472–488. doi: 10.1039/c2pp05399c.
  Gryaznov, S. M., & Letsinger, R. L. (1991). Synthesis of oligonucleotides via monomers with unprotected bases. Journal of the American Chemical Society, 113, 5876–5877. doi: 10.1021/ja00015a059.
  Guerlavais, T., Meyer, A., Imbach, J.‐L., & Morvan, F. (2001). Use of 2‐(tert‐butyldiphenylsilyloxymethyl) benzoyl as N‐protecting group for the synthesis of prooligonucleotides. Bioorganic & Medicinal Chemistry Letters, 11, 2813–2816. doi: 10.1016/S0960‐894X(01)00515‐7.
  Guerlavais, T., Meyer, A., & Morvan, F. (2002). Efficient and low cost synthesis of 2‐(tert‐butyldiphenylsilyloxymethyl)benzoyl chloride for the protection of nucleobases. Journal Chemical Research, 11, 606–607. doi: 10.3184/030823402103171203.
  Guerlavais‐Dagland, T., Meyer, A., Imbach, J.‐L., & Morvan, F., (2003). Fluoride‐labile protecting groups for the synthesis of base‐sensitive methyl‐SATE oligonucleotide prodrugs. European Journal of Organic Chemistry, 2003, 2327–2335. doi: 10.1002/ejoc.200300069.
  Hagen, M. D., & Chládek, S. (1989). General synthesis of 2′(3′)‐O‐aminoacyl oligoribonucleotides. The protecion of the guanine moiety. The Journal of Organic Chemistry, 54, 3189–3195. doi: 10.1021/jo00274a041.
  Hall, R. H., Todd, A. R., & Webb, R. F. (1957). Nucleotides. Part XLI. Mixed anhydrides as intermediates in the synthesis of dinucleoside phosphates. Journal of the Chemical Society, 3291–3296. doi: 10.1039/JR9570003291.
  Hayakawa, Y., Hirose, M., & Noyori, R. (1993). O‐Allyl protection of guanine and thymine residues in oligodeoxyribonucleotides. The Journal of Organic Chemistry, 58, 5551–5555. doi: 10.1021/jo00072a050.
  Hayakawa, Y., Kato, H., Uchiyama, M., Kajino, H., & Noyori, R. (1986). Allyloxycarbonyl group: A versatile blocking group for nucleotide synthesis. The Journal of Organic Chemistry, 51, 2400–2402. doi: 10.1021/jo00362a052.
  Hayakawa, Y., Kawai, R., & Kataoka, M. (2001). Nucleotide synthesis via methods without nucleoside‐base protection. European Journal of Pharmaceutical Sciences, 13, 5–16. doi: 10.1016/S0928‐0987(00)00202‐5.
  Hayakawa, Y., Wakabayashi, S., Kato, H., & Noyori, R. (1990). The allylic protection method in solid‐phase oligonucleotide synthesis. An efficient preparation of solid‐anchored DNA oligomers. Journal of the American Chemical Society, 112, 1691–1696. doi: 10.1021/ja00161a006.
  Heikkilä, J., & Chattopadhyaya, J. (1983). The 9‐fluorenylmethoxycarbonyl (Fmoc) group for the protection of amino functions of cytidine, adenosine, guanosine and their 2′‐deoxysugar derivatives. Acta Chemica Scandinavica, B37, 263–265. doi: 10.3891/acta.chem.scand.37b‐0263.
  Hemphill, J., Liu, Q., Rajendra Uprety, R., Samanta, S., Tsang, M., Rudolph Juliano, R. L., & Deiters, A. (2015). Conditional control of alternative splicing through light‐triggered splice‐switching oligonucleotides. Journal of the American Chemical Society, 137, 3656–3662. doi: 10.1021/jacs.5b00580.
  Himmelsbach, F., Schulz, B. S., Trichtinger, T., Charubala, R., & Pfleiderer, W. (1984). The p‐nitrophenylethyl (NPE) group. A versatile new blocking group for phosphate and aglycone protection in nucleosides and nucleotides. Tetrahedron, 40, 59–72. doi: 10.1016/0040‐4020(84)85103‐0.
  Holy, A., & Zemlicka, J. (1969). Oligonucleotidic compounds. XXXIII. A study on hydrolysis of N‐dimethylaminomethylenecytidine, ‐adenosine, ‐guanosine, and related 2′‐deoxy compounds. Collection of Czechoslovak Chemical Communications, 34, 2449–2458. doi: 10.1135/cccc19692449.
  Honda, S., Urakami, K., Koura, K., Terada, K., Sato, Y., Kohno, K., … Hata, T. (1984). Synthesis of oligoribonucleotides by use of S,S‐diphenyl N‐monomethoxytrityl ribonucleoside 3′‐phosphorodithioates. Tetrahedron, 40, 153–163. doi: 10.1016/0040‐4020(84)85114‐5.
  Huynh‐Dinh, T., Langlois d'Estaintot, B., Allard, P., & Igolen, J. (1985). Synthèse simplifièe de sondes mixtes avec des triazolo‐nucléosides. Tetrahedron Letters, 26, 431–434. doi: 10.1016/S0040‐4039(00)61903‐2.
  Hyodo, M., & Hayakawa, Y. (2006). Nucleobase protection with allyloxycarbonyl. Current Protocols in Nucleic Acid Chemistry, 23, 2.12.1–2.12.26. doi: 10.1002/0471142700.nc0212s23.
  Igolen, J., & Morin, C. (1980). Rapid synthesis of protected 2′‐deoxycytidine derivatives. The Journal of Organic Chemistry, 45, 4802–4804. doi: 10.1021/jo01311a061.
  Ito, T., Ueda, S., & Takaku, H. (1986). (Methoxyethoxy)methyl group: New amide and hydroxyl protecting groups of uridine in oligonucleotide synthesis. The Journal of Organic Chemistry, 51, 931–933. doi: 10.1021/jo00356a033.
  Iwase, R., Kitani, A., Yamaoka, T., & Murakami, A. (2003). Synthesis of antisense oligonucleotides containing photocleavable protecting groups on the thymine bases and their photoinduced duplex formation. Nucleic Acids Research. Supplement No, 3, 61–62. doi: 10.1093/nass/49.1.15.
  Iyer, R. P., & Beaucage, S. L. (1999). Oligonucleotide synthesis. In E. T. Kool (Ed.), Comprehensive Natural Products Chemistry (Vol. 7: DNA and Aspects of Molecular Biology pp. 105‐152). New York: Elsevier Science Publishing.
  Iyer, R. P., Yu, D., Habus, I., Ho, N. H., Johnson, S., Devlin, T., … Agrawal, S. (1997). N‐Pent‐4‐enoyl (PNT) group as a universal nucleobase protector: Applications in the rapid and facile synthesis of oligonucleotides, analogs and conjugates. Tetrahedron, 53, 2731–2750. doi :10.1016/S0040‐4020(97)00048‐3.
  Jones, S. S., Reese, C. B., Sibanda, S., & Ubasawa, A. (1981). The protection of uracil and guanine residues in oligonucleotide synthesis. Tetrahedron Letters, 22, 4755–4758. doi: 10.1016/S0040‐4039(01)83032‐X.
  Kaloudis, P., Paris, C., Vrantza, D., Encinas, S., Perez‐Ruiz, R., Miranda, M. A., & Gimisis, T. (2009). Photolabile N‐hydroxypyrid‐2(1H)‐one derivatives of guanine nucleosides: A new method for independent guanine radical generation. Organic & Biomolecular Chemistry, 7, 4965–4972. doi: 10.1039/B909138F.
  Kamaike, K., Hasegawa, Y., & Ishido, Y. (1988). A simple, preparative procedure for N3‐anisoyluridine and O6‐diphenylcarbamoylguanosine 2′‐O‐(tetrahydropyran‐2‐yl) derivatives via the corresponding 3′,5′‐dibenzoates. Nucleosides & Nucleotides, 7, 37–43. doi: 10.1080/07328318808068701.
  Kamimura, T., Masegi, T., Urakami, K., Honda, S., Sekine, M., & Hata, T. (1983a). A new protecting tactics for the uracil residue in oligoribonucleotide synthesis. Chemistry Letters, 1051–1054. doi: 10.1246/cl.1983.1051.
  Kamimura, T., Tsuchiya, M., Koura, K., Sekine, M., & Hata, T. (1983b). Diphenylcarbamoyl and propionyl groups: A new combination of protecting groups on the guanine residue. Tetrahedron Letters, 24, 2775–2778. doi: 10.1016/S0040‐4039(00)88019‐3.
  Kaplan, J. H., Forbush, B. III, and Hoffman, J. F. (1978). Rapid photolatic release of adenosine 5¢‐triphosphate from a protected analogue: Utilization by the Na:K pump of human red blood cell ghosts. Biochemistry, 17, 1929–1935. doi: 10.1021/bi00603a020.
  Karpeisky, A., Sweedler, D., Haeberli, P., Read, J., Jarvis K., & Beigelman, L. (2002). Scaleable and efficient synthesis of 2′‐deoxy‐2′‐N‐phthaloyl nucleoside phosphoramidites for oligonucleotide synthesis. Bioorganic & Medicinal Chemistry Letters, 12, 3345–3347. doi: 10.1016/S0960‐894X(02)00744‐8.
  Khorana, H. G. (1979). Total synthesis of a gene. Science, 203, 614–625. doi: 10.1126/science.366749.
  Klan, P., Šolomek, T., Bochet, C. G., Blanc, A., Givens, R., Rubina, M., … Wirz, J. (2013). Photoremovable protecting groups in chemistry and biology: Reaction mechanisms and efficacy. Chemical Reviews, 113, 119–191. doi: 10.1021/cr300177k.
  Kobori, A., Miyata, K., Ushioda, M., Seio, K., & Sekine, M. (2002). A new method for the synthesis of oligodeoxyribonucleotides containing 4‐N‐alkoxycarbonyldeoxycytidine derivatives and their hybridization properties. The Journal of Organic Chemistry, 67, 476–485. doi: 10.1021/jo010813l.
  Kohli, V., & Kumar, A. (1979). Synthesis of deoxypolynucleotides ‐ a novel protecting group for deoxyguanosine. Indian Journal of Chemistry Section B: Organic Chemistry including Medicinal Chemistry, 18B, 272–273.
  Köster, H., Kulikowski, K., Liese, T., Heikens, W., & Kohli, V. (1981). N‐acyl protecting groups for deoxynucleosides. A quantitative and comparative study. Tetrahedron, 37, 363–369. doi: 10.1016/S0040‐4020(01)92022‐8.
  Krecmerová, M., Hrebabecky, H., & Holy, A. (1990). Synthesis of 5′‐O‐phosphonomethyl derivatives of pyridine 2′‐deoxynucleosides. Collection of Czechoslovak Chemical Communications, 55, 2521–2536. doi: 10.1135/cccc19902521.
  Kuijpers, W. H. A., Huskens, J., & van Boeckel, C. A. A. (1990). The 2‐(acetoxymethyl)benzoyl (AMB) group as a new base‐protecting group, designed for the protection of phosphate modified oligonucleotides. Tetrahedron Letters, 31, 6729–6732. doi: /10.1016/S0040‐4039(00)97159‐4.
  Kume, A., Iwase, R., Sekine, M., & Hata, T. (1984). Cyclic diacyl groups for protection of the N6‐amino group of deoxyadenosine in oligodeoxynucleotide synthesis. Nucleic Acids Research, 12, 8525–8538. doi: 10.1093/nar/12.22.8525.
  Kume, A., Sekine, M., & Hata, T. (1982). Phthaloyl group: A new amino protecting group of deoxyadenosine in oligonucleotide synthesis. Tetrahedron Letters, 23, 4365–4368. doi: 10.1016/S0040‐4039(00)85601‐4.
  Lavergne, T., Baraguey, C., Dupouy, C., Parey, N., Wuensche, W., Sczakiel, G., … Debart, F. (2011). Synthesis and preliminary evaluation of pro‐RNA 2′‐O‐masked with biolabile pivaloyloxymethyl groups in an RNA interference Assay. The Journal of Organic Chemistry, 76, 5719–5731. doi: 10/1021/jo200826h.
  Letsinger, R. L., & Lunsford, W. B. (1976). Synthesis of thymidine oligonucleotides by phosphite triester intermediates. Journal of the American Chemical Society, 98, 3655–3661. doi: 10.1021/ja00428a045.
  Letsinger, R. L., & Ogilvie, K. K. (1969). Synthesis of oligothymidylates via phosphotriester intermediates. Journal of the American Chemical Society, 91, 3350–3355. doi: 10.1021/ja01040a042.
  Li, B. F. L., Reese, C. B., & Swann, P. F. (1987). Synthesis and characterization of oligodeoxynucleotides containing 4‐O‐methylthymine. Biochemistry, 26, 1086–1093. doi: 10.1021/bi00378a015.
  Liang, H., Hu, L., & Corey E. J. (2011). di‐tert‐Butylisobutylsilyl, another useful protecting group. Organic Letters, 13, 4120–4123. doi: 10.1021/ol201640y.
  Lin, X, (2013). Oligodeoxynucleotide synthesis using protecting groups and a linker cleavable under non‐nucleophilic conditions. PhD dissertation, Michigan Technological University, Houghton, Michigan.
  Lin, X., Chen, J., Shahsavari, S., Green, N., Goyal, D., & Fang, S. (2016). Synthesis of oligodeoxynucleotides containing electrophilic groups. Organic Letters, 18, 3870–3873. doi: 10.1021/acs.orglett.6b01878.
  Liu, Q., & Deiters, A. (2014). Optochemical control of deoxyoligonucleotide function via a nucleobase‐caging approach. Accounts of Chemical Research, 47, 45–55. doi: 10.1021/ar400036a.
  Lusic, H., & Deiters, A. (2006). A new photocaging group for aromatic N‐heterocycles. Synthesis, 13, 2147–2150. doi: 10.1055/s‐2006‐942424.
  Lusic, H., Lively, M. O. A., & Deiters, A. (2008). Light‐activated deoxyguanosine: Photochemical regulation of peroxidase activity. Molecular Biosystems, 4, 508–511. doi: 10.1039/b800166a.
  Lusic, H., Uprety, R., & Deiters, A. (2010). Improved synthesis of the two‐photon caging group 3‐nitro‐2‐ethyldibenzofuran and its application to a caged thymidine phosphoramidite. Organic Letters, 12, 916–919. doi: 10.1021/ol902807q.
  Lusic, H., Young, D. D., Lively, M. O., & Deiters, A. (2007). Photochemical DNA activation. Organic Letters, 9, 1903–1906. doi: 10.1021/ol070455u.
  MacMillan, A. M., & Verdine, G. L. (1991). Engineering tethered DNA molecules by the convertible nucleoside approach. Tetrahedron, 47, 2603–2616. doi: 10.1016/S0040‐4020(01)81793‐2.
  Mag, M., & Engels, J. W. (1988). Synthesis and structure assignments of amide protected nucleosides and their use as phosphoramidites in deoxyoligonucleotide synthesis. Nucleic Acids Research, 16, 3525–3543. doi: 10.1093/nar/16.8.3525.
  Manoharan, M., Prakash, T. P, Barber‐Peoch, I., Balkrishen, B., Vasquez, G., Ross, B. S., & Cook, P. D. (1999). N‐2(‐cyanoethoxycarbonyloxy)succinimide: A new reagent for protection of amino groups in oligonucleotides. The Journal of Organic Chemistry, 64, 6468–6472. doi: 10.1021/jo982299y.
  Marugg, J. E., Tromp, M., Jhurani, P., Hoyng, C. F., van der Marel, G. A., & van Boom, J. H. (1984). Synthesis of DNA fragments by the hydroxybenzotriazole phosphodiester approach. Tetrahedron, 40, 73–78. doi: 10.1016/0040‐4020(84)85104‐2.
  Matteucci, M. D., & Caruthers, M. H. (1980). The synthesis of oligodeoxypyrimidines on a polymer support. Tetrahedron Letters, 21, 719–722. doi: 10.1016/S0040‐4039(00)71455‐9.
  McBride, L. J., Eadie, J. S., Efcavitch, J. W., & Andrus, A. (1987). Base modification and the phosphoramidite approach. Nucleosides & Nucleotides, 6, 297–300. doi: 10.1080/07328318708056208.
  McBride, L. J., Kierzek, R., Beaucage, S. L., & Caruthers, M. H. (1986). Amidine protecting groups for oligonucleotide synthesis. Journal of the American Chemical Society, 108, 2040–2048. doi: 10.1021/ja00268a052.
  Menge, C., & Heckel, A. (2011). Coumarin‐Caged dG for improved wavelength‐selective uncaging of DNA. Organic Letters, 13, 4620–4623. doi: 10.1021/ol201842x.
  Merk, C., Reiner, T., Kvasuk, E., & Pfleiderer, W. (2000). The 2‐cyanoethyl and (2‐cyanoethoxy)carbonyl group for base protection in nucleoside and nucleotide chemistry. Helvetica Chimica Acta, 83, 3198–3210. doi: /10.1002/1522‐2675(20001220)83:12<3198.
  Michelson, A. M., & Todd, A. R. (1955). Nucleotides. Part XXXII. Synthesis of a dithymidine dinucleotide containing a 3′:5′‐internucleotidic linkage. Journal of the Chemical Society, 2632–2638. doi: 10.1039/JR9550002632.
  Mikat, V., & Heckel, A. (2007). Light dependent RNA interference with nucleobase‐caged SiRNAs. RNA, 13, 2341–2347. doi: 10.1261/rna.753407.
  Mishra, R. K., & Misra, K. (1986). Improved synthesis of oligodeoxyribonucleotide using 3‐methoxy‐4‐phenoxybenzoyl group for amino protection. Nucleic Acids Research, 14, 6197–6213. doi: 10.1093/nar/14.15.6197.
  Mishra, R., Mishra, S., Diwedi, V., & Misra, K. (2006). A strategy for selective N‐acylation of purine and pyrimidine bases of deoxy and ribo nucleosides. Nucleic Acids Symposium Series, 50, 7–8. doi: 10.1093/nass/nrl1004.
  Miyata, K., Tamamushi, R., Ohkubo, A., Taguchi, H., Seio, K., & Sekine, M. (2004). Synthesis and hybridization affinity of oligodeoxyribonucleotides incorporating 4‐N‐(N‐arylcarbamoyl)deoxycytidine derivatives. Tetrahedron Letters, 45, 9365–9368. doi: 10.1016/j.tetlet.2004.10.116.
  Momotake, A., Lindegger, N., Niggli, E., Barsotti, R. J., & Ellis‐Davies, G. C. R. (2006). The nitrodibenzofuran chromophore: A new caging group for ultra‐efficient photolysis in living cells. Nature Methods, 3, 35–40. doi: 10.1038/NMETH821.
  Mullah, B., Andrus, A., Zhao, H., & Jones, R. A. (1995). Oxidative conversion of N‐dimethylformamidine nucleosides to N‐cyano nucleosides. Tetrahedron Letters, 36, 4373–4376. doi: 10.1016/0040‐4039(95)00816‐U.
  Nagaich, A. K., & Misra, K. (1989). Highly efficient synthesis of oligodeoxyribonucleotides using α‐phenyl cinnamoyl group for selective amino protection. Nucleic Acids Research, 17, 5125–5134. doi: 10.1093/nar/17.13.5125.
  Nahar, P. (1997). Microwaves ‐ A powerful tool for the base protection of cytidine. Tetrahedron Letters, 41, 7253–7254. doi: 10.1016/S0040‐4039(97)01684‐5.
  Narang, S. A., Itakura, K., & Wightman, R. H. (1972). A simplification in the synthesis of deoxyribooligonucleotides. Canadian Journal of Chemistry, 50, 769–770. doi: 10.1139/v72‐118.
  Nielsen, J., Dahl, O., Remaud, G., & Chattopadhyaya, J. (1987). Phosphitylation of guanine or inosine bases during the preparation of nucleoside phosphoramidites. Isolation of model products as thiophosphoric amide derivatives and structure elucidation by 15N NMR spectroscopy. Acta Chemica Scandinavica, B41, 633–639. doi: 10.3891/acta.chem.scand.41b‐0633.
  Nowak, I., & Robins, M. J. (2003). Protection of the amino group of adenosine and guanosine derivatives by elaboration into a 2,5‐dimethylpyrrole moiety. Organic Letters, 18, 3345–3348. doi: 10.1021/ol035264f.
  Nyilas, A., Földesi, A., & Chattopadhyaya, J. (1988). Arenesulfonylethoxycarbonyl—A set of amino protecting groups for DNA and RNA synthesis. Nucleosides & Nucleotides, 7, 787–793. doi: 10.1080/07328318808056331.
  Nyilas, A., Zhou, X.‐X., Welch, C. J., & Chattopadhyaya, J. (1987). A versatile strategy for the O4‐protection and modification of the lactam function of uridine and uridylic acid. Nucleic Acids Research Symposium Series, 18, 157–160.
  Ogilvie, K. K., Nemer, M. J., Hakimelahi, G. H., Proba, Z. A., & Lucas, M. (1982). N‐Levulination of nucleosides. Tetrahedron Letters, 23, 2615–2618. doi: 10.1016/S0040‐4039(00)87411‐0.
  Ohkubo, A., Kasuya, R., Miyata, K., Taguchi, H., & Sekine, M. (2007). Development of a new method for the synthesis of oilgodeoxynucleotides by the use of carbamoyl‐type protecting groups. Nucleic Acids Symposium Series, 51, 131–132. doi: 10.1093/nass/nrm066.
  Ohkubo, A., Kasuya, R., Miyata, K., Tsunoda, H., Seio H., & Sekine, M. (2009). New thermolytic carbamoyl groups for the protection of nucleobases. Organic & Biomolecular Chemistry, 7, 687–694. doi: 10.1039/B816831h.
  Ohkubo, A., Kasuya, R., Sakamoto, K., Miyata, K., Taguchi, H., Nagasawa, H., … Sekine, M. (2008). Protected DNA probes capable of strong hybridization without removal of base protecting groups. Nucleic Acids Research, 36, 1952–1964. doi: 10.1093/nar/gkm927.
  Ohkubo, A., Kuwayama, Y., Nishino, Y., Tsunoda, H., Seio, K., & Sekine M. (2010). Oligonucleotide syntheis involving deprotection of amidine‐type protecting groups for nucleobases under acidic conditions. Organic Letters, 12, 2496–2499. doi: 10:1021/0110676j.
  Ohkubo, A., Sakamoto, K., Miyata, K.‐I., Taguchi, H., Seio, K., & Sekine, M. (2005). Convenient synthesis of N‐unprotected deoxynucleoside 3′‐phosphoramidite building blocks by selective deacylation of N‐acylated species and their facile conversion to other N‐functionalized derivatives. Organic Letters, 24, 5389–5392. doi: 10.1021/ol051949z.
  Ohkubo, A., Seio, K., & Sekine, M. (2006). DNA synthesis without base protection using the phosphoramidite approach. Current Protocols in Nucleic Acids Chemistry, 26, 3.15.1–3.15.22. doi: 10.1002/0471142700.nc0315s26.
  Ohtsuki, T., Shigeto, K., Sae, N., Yoshio, K., Masahiko, S., & Kazunori W. (2016). Phototriggered protein synthesis by using (7‐dimethylaminocoumarin‐4‐yl)methoxycarbonyl‐caged amniacyl tRNAs. Nature Communications, 7, 12502–12502. doi: 10.1038/ncomms12501.
  Oivanen, M., Lönnberg, H., Zhou, X. X., & Chattopadhyaya, J. (1987). Acidic hydrolysis of 6‐substituted 9‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)purines and their 9‐(1‐alkoxyethyl) counterparts: Kinetics and mechanism. Tetrahedron, 43, 1133–1140. doi: 10.1016/s0040‐4020(01)90052‐3.
  Paul, C. H., & Royappa, A. T. (1996). Acid binding and detritylation during oligonucleotide synthesis. Nucleic Acids Research, 24, 3048–3052. doi: 10.1093/nar/24.15.3048.
  Pfister, M., Farkas, S., Charubala, R., & Pfleiderer, W. (1988). Recent progress in oligoribonucleotide synthesis. Nucleosides & Nucleotides, 7, 595–600. doi: 10.1080/07328318808056292.
  Pfister, M., & Pfleiderer, W. (1989). New results in oligoribonucleotide synthesis. Nucleosides & Nucleotides, 8, 1001–1006. doi: 10.1080/07328318908054263.
  Pfleiderer, W. (2007). Universal 2‐(4‐nitrophenyl)ethyl and 2‐(4‐nitrophenyl)ethoxycarbonyl protecting groups for nucleosides and nucleotides. Current Protocols in Nucleic Acid Chemistry, 30, 2.13.1–2.13.25. doi: 10.1002/0471142700.nc021s30.
  Pfleiderer, W., Himmelsbach, F., Charubala, R., Schirmeister, H., Beiter, A., Schulz, B., & Trichtinger, T. (1985). The p‐nitrophenylethyl group—An universal blocking group in nucleoside and nucleotide chemistry. Nucleosides & Nucleotides, 4, 81–94. doi: 10.1080/07328318508077832.
  Pitsch, S. (2001). Protecting groups for the synthesis of ribonucleic acids. Chimia, 55, 320–324.
  Pon, R. T., Damha, M. J., & Ogilvie, K. K. (1985a). Necessary protection of the O6‐position of guanosine during the solid phase synthesis of oligonucleotides by the phosphoramidite approach. Tetrahedron Letters, 26, 2525–2528. doi: 10.1016/S0040‐4039(00)98827‐0.
  Pon, R. T., Damha, M. J., & Ogilvie, K. K. (1985b). Modification of guanine bases by nucleoside phosphoramidite reagents during the solid phase synthesis of oligonucleotides. Nucleic Acids Research, 13, 6447–6465. doi: 10.1093/nar/13.18.6447.
  Porcher, S., & Pitsch, S. (2005). Synthesis of 2′‐O‐[triisopropylsilyl)oxy]methyl({=tom)‐protected ribonucleoside phosphoramidites containing various nucleobase analogs. Helvetica Chimica Acta, 88, 2683–2704. doi: 10.1002/hlca.200590209.
  Prasad, A. K., & Wengel, J. (1996). Enzyme‐mediated protecting group chemistry on the hydroxyl groups of nucleosides. Nucleosides & Nucleotides, 15, 1347–1359. doi: 10.1080/07328319608002435.
  Rad, M. N. S., Behrouz, S., Asrari, Z., & Khalafi‐Nezhad, A. (2014). Simple and regioeselective one‐pot procedure for the direct N‐acylation of some purine and pyrimidine nucleobases via carboxylic acids using cyanuric chloride. Monatshefte Fur Chemie, 145, 1933–1940. doi: 10.1007/s00706‐014‐1270‐1.
  Rao, T. S., Reese, C. B., Serafinowska, H. T., Takaku, H., & Zappia, G. (1987). Solid‐phase synthesis of the 3′‐terminal nonadecaribonucleoside octadecaphosphate sequence of yeast alanine transfer ribonucleic acid. Tetrahedron Letters, 28, 4897–4900. doi: 10.1016/S0040‐4039(00)96655‐3.
  Rao, N. S., Kumar, P., Chauhan, V. K., Garg, B. S., & Gupta, K. C. (2002). Microwave‐assisted high yielding synthesis of N‐protected 2′‐deoxyribonucleosides useful for oligonucleotide synthesis. Nucleosides & Nucleotides & Nucleic Acids, 21, 393–400. doi: 10.1081/NCN‐120006833.
  Reddy, M. P., Hanna, N. B., & Farooqui, F. (1994). Fast cleavage and deprotection of oligonucleotides. Tetrahedron Letters, 35, 4311–4314. doi: 10.1016/S0040‐4039(00)73341‐7.
  Reese, C. B. (1978). The chemical synthesis of oligo‐ and poly‐nucleotides by the phosphotriester approach. Tetrahedron, 34, 3143–3179. doi: 10.1016/0040‐4020(78)87013‐6.
  Reese, C. B., & Skone, P. A. (1984). The protection of thymine and guanine residues in oligodeoxyribonucleotide synthesis. Journal of the Chemical Society Perkin Transactions, 1, 1263–1271. doi: 10.1039/P19840001263.
  Reese, C. B., & Ubasawa, A. (1980). Reaction between 1‐arenesulphonyl‐3‐nitro‐1,2,4‐triazoles and nucleoide residues. Elucidation of the nature of side‐reactions during oligonucleotide synthesis. Tetrahedron Letters, 21, 2265–2268. doi: 10.1016/0040‐4039(80)80020‐7.
  Reid, A. K., McHugh, C. J., Richie, G., & Graham, D. (2006). Electron‐defecient benzotriazole for the selectie acetylation of nucleosides. Tetrahedron Letters, 47, 4201–4203. doi: 10.1016/j.tetlet.2006.04.079.
  Rigoli, J. W., Østergaard, M. E., Canady, K. M., Guenther, D. C., & Hrdlicka, P. J. (2009). Selective deacylation of peracylated ribonucleosides. Tetrahedron Letters, 50, 1751–1753. doi: 10.1016/j.tetlet.2009.01.147.
  Rode, A. B., Son, S. J., & Hong, I. S. (2010). An Efficient one‐pot N‐acylation of deoxy‐ and ribo‐cytidine using carboxylic acids activated in situ with 2‐chloro‐4,6‐dimethoxy‐1,3,5‐triazine. Bulletin of The Korean Chemical Society, 31, 2061–2064. doi: 10.106/j.jinorgbio.2015.03.010.
  Rodrigues‐Correia, A., Knapp‐Bühle, D., Engels, J. W., & Heckel, A. (2014). Selective uncaging of DNA through reaction rate selectivity. Organic Letters, 16, 5128–5131. doi: 10.1021/ol502478g.
  Rodrigues‐Correia, A., Seyfried, P., & Heckel, A. (2014). Wavelength‐selective uncaging of oligonucleotides. Current Protocols in Nucleic Acid Chemistry, 57, 6.11.1‐6.11.32. doi: 10.1002/0471142700.nc0611s57.
  Rodrigues‐Correia, A., Stoess, T., Wilhem, J., Berlin, B., & Heckel, A. (2013). Rapid synthetic access to caged RNA. Indian Journal of Chemistry, 52A, 1014–1018.
  Rodrigues‐Correia, A., Weyel, X. M. M., & Heckel, A. (2013). Four levels of wavelength‐selective uncaging for oligonucleotides. Organic Letters, 15, 5500–5503. doi: 10.1021/ol402657j.
  Romero, R., Stein, R., Bull, H. G., & Cordes, E. H. (1978). Secondary deuterium isotope effects for acid‐catalyzed hydrolysis of inosine and adenosine. Journal of the American Chemical Society, 100, 7620–7624. doi: 10.1021/ja00492a030.
  Ruble, B. K., Yeldell, S. B., & Dmochowski, I. J. (2015). Caged oligonucleotides for studying biological system. The Journal of Biological Chemistry, 150, 182–188. doi: 10.1016/j.jinorgbio.2015.03.010.
  Saenger, W. (1984). Principles of Nucleic Acids Structure. New York: Springer‐Verlag.
  Sanghvi, Y. S., Misra, K., & Tripathi, S. (2002). Process for regeioselective N‐acylation of purine nucleoides using polymer supported cyclohexylurea. PCT Int Appl: WO 2002083702.
  Scalfi‐Happ, C., Happ, E., & Chládek, S. (1987). New approach to the synthesis of 2′ (3′)‐O‐aminoacyl‐oligoribonucleotides related to the 3′‐terminus of aminoacyl transfer ribonucleic acid. Nucleosides & Nucleotides, 6, 345–348. doi: 10.1080/07328318708056218.
  Schäfer, F., Joshi, K. B., Fichte, M. A. H., Mack, T., Wachtveitl, J., & Heckel, A. (2011). Wavelength‐selective uncaging of dA and dC residues. Organic Letters, 13, 1450–1453. doi: 10.1021/ol200141v.
  Schaller, H., Weimann, G., Lerch, W. B., & Khorana, H. G. (1963). Studies on polynucleotides. XXIV. The stepwise synthesis of specific deoxyribopolynucleotides (4). Protected derivatives of deoxyribonucleosides and new syntheses of deoxyribonucleoside‐3′‐phosphates. Journal of the American Chemical Society, 85, 3821–3827. doi: 10.1021/ja00906a021.
  Schirmeister, H., & Pfleiderer, W. (1987). Base labile protecting groups for hydroxyl functions in ribonucleosides and deoxyribonucleosides. Nucleosides & Nucleotides, 6, 501–503. doi: 10.1080/07328318708056269.
  Schulhof, J. C., Molko, D., & Teoule, R. (1987). Facile removal of new base protecting groups useful in oligonucleotide synthesis. Tetrahedron Letters, 28, 51–54. doi: 10.1016/S0040‐4039(00)95646‐6.
  Seio, K., Ohno, Y., Ohno, K., Takeshita, L., Kanamori, T., Masaki, Y., & Sekine, M. (2016). Photo‐controlled binding of MutS to photo‐caged DNA duplexes incorporating 4‐O‐(2‐nitrobenzyl) or 4‐O‐[2‐(2‐nitrophenyl)propyl]thymidine. Bioorganic & Medicinal Chemistry Letters, 26, 4861–4863. doi: 10.1016/j.bmcl.2016.07.075.
  Sekine, M. (1989). General method for the preparation of N3‐ and O4‐substituted uridine derivatives by phase‐transfer reactions. The Journal of Organic Chemistry, 54, 2321–2326. doi: 10.1021/jo00271a015.
  Sekine, M. (2004). DNA synthesis without base protection. Current Protocols in Nucleic Acids Chemistry, 18, 3.10.1–3.10.15. doi: 10.1002/0471142700.nc0310s18.
  Sekine, M., Masuda, N., & Hata, T. (1985). Introduction of the 4,4′,4′‐tris(benzoyloxy)trityl group into the exo amino groups of deoxyribonucleosides and its properties. Tetrahedron, 41, 5445–5453. doi: 10.1016/S0040‐4020(01)91344‐4.
  Shabarova, Z., & Bogdanov, A. (1994). Advanced organic chemistry of nucleic acids. New York: VCH Publishers.
  Shao, Q., & Xing, B. (2010). Photoactive molecules for applications in molecular imaging and cell biology. Chemical Society Reviews, 39, 2835–2846. doi: 10.1039/b915574k.
  Shimidzu, T., & Letsinger, R. L. (1968). Synthesis of deoxyguanylyldeoxyguanosine on an insoluble polymer support. The Journal of Organic Chemistry, 33, 708–711.
  Shimizu, M., & Sodeoka, M. (2007). Convenient method for the preparation of carbamates, carbonates, and thicarbonates. Organic Letters, 9, 5231–5234. doi: 10.1021/ol7024108.
  Sikehi, S. A., & Hultin, P. G. (2006). Solventless protocol for efficient bis‐N‐Boc protection of adenosine, cytidine, and guanosine derivatives. The Journal of Organic Chemistry, 71, 5888–5891. doi: 10.1021/jo060430t.
  Sinha, N. D., Davis, P., Schultze, L. M., & Updhya, K. (1995). A simple method for N‐acylation of adenosine and cytidine nucleosides using carboxylic acids activated in‐situ with carbonyldiimidazole. Tetrahedron Letters, 36, 9277–9280. doi: 10.1016/0040‐4039(95)02011‐D.
  Sinha, N. D., Davis, P., Usman, N., Pérez, J., Hodge, R., Kremsky, J., & Casale, R. (1993). Labile exocyclic amine protection of nucleosides in DNA, RNA and oligonucleotide analog synthesis facilitating N‐deacylation, minimizing depurination and chain degradation. Biochimie, 75, 13–23. doi: 10.1016/0300‐9084(93)90019‐O.
  Singh, R. K., & Misra, K. (1988). Improvements in oligodeoxyribonucleotide synthesis using phenoxyacetyl as amino protecting group. Indian Journal of Chemistry, 27B, 409‐417.
  Smith, C. A., Xu Y. Z., & Swann, P. F. (1990). Solid‐phase synthesis of oligodeoxynucleotides containing O6‐alkylguanine. Carcinogenesis, 11, 811–816. doi: 10.1093/carcin/11.5.811.
  Smrt, J., & Sorm, F. (1967). Oligonucleotidic compounds. XVIII. Synthesis of guanylyl‐(3′‐5′)‐uridylyl‐(3′‐5′)‐arabinofuranosyluracil and guanylyl‐(3′‐5′)‐uridylyl‐(3′‐5′)‐arabinofurano‐sylcytosine. Collection of Czechoslovak Chemical Communications, 32, 3169–3176. doi: 0.1135/cccc19673169.
  Somoza, A. (2008). Protecting groups for RNA synthesis: An increasing need for selective preparative methods. Chemical Society Reviews, 37, 2668–2675. doi: 10.1039/B809851D.
  Sonveaux, E. (1986). The organic chemistry underlying DNA synthesis. Bioorganic Chemistry, 14, 274–325. doi: 10.1016/0045‐2068(86)90038‐6.
  Sproat, B. S., Iribarren, A. M., Guimil Garcia, R., & Beijer, B. (1991). New synthetic routes to synthons suitable for 2′‐O‐allyloligoribonucleotide assembly. Nucleic Acids Research, 19, 733–738. doi: 10.1093/nar/19.4.733.
  Stutz, A., Höbartner, C., & Pitsch, S. (2000). Novel fluoride‐labile nucleobase‐protecting groups for the synthesis of 3′(2′)‐O‐aminoacylated RNA sequences. Helvetica Chimica Acta, 83, 2477–2503. doi: 10.1002/1522‐2675(20000906)83:93.0.CO;2‐9.
  Stutz, A., & Pitsch, S. (1999). Automated RNA synthesis with photocleavable sugar and nucleobase protecting groups. Synlett, S1, 930–934. doi: 10.1055/s‐1999‐3098.
  Sung, W. L. (1982). Synthesis of 4‐(1,2,4‐triazol‐1‐yl)pyrimidin‐2(1H)‐one‐ribonucleotide and its application in synthesis of oligoribonucleotides. The Journal of Organic Chemistry, 47, 3623–3628. doi: 10.1021/jo00140a005.
  Suzuki, T., Ohsumi, S., & Makino, K. (1994). Mechanistic studies on depurination and apurinic site chain breakage in oligodeoxyribonucletides. Nucleic Acids Research, 22, 4997–5003. doi: 10.1093/nar/22.23.4997.
  Takaku, H., Imai, K., & Nagai, M. (1988). Triphenylmethanesulfenyl group. A new protecting group for the uracil residue in oligoribonucleotide synthesis. Chemistry Letters, 857–860. doi: 10.1246/cl.1988.857.
  Tang, X., Zhang, T., Sun, J., Wang, Y., Wu, J., & Zhang, L. (2013). Caged nucleotides/nucleosides and their photochemical biology. Organic & Biomolecular Chemistry, 11, 7814–7824. doi: 10.1039/C3OB41735B.
  Tanimura, H., Fukazawa, T., Sekine, M., Hata, T., Efcavitch, J. W., & Zon, G. (1988). The practical synthesis of RNA fragments in the solid phase approach. Tetrahedron Letters, 29, 577–578. doi: 10.1016/S0040‐4039(00)80154‐9.
  Ti, G. S., Gaffney, B. L., & Jones, R. A. (1982). Transient protection: Efficient one‐flask synthesis of protected deoxynucleosides. Journal of the American Chemical Society, 104, 1316–1319. doi: 10.1021/ja00369a029.
  Trichtinger, T., Charubala, R., & Pfleiderer, W. (1983). Synthesis of O6‐p‐nitrophenylethyl guanosine and 2′‐deoxyguanosine derivatives. Tetrahedron Letters, 24, 711–714. doi: 10.1016/S0040‐4039(00)81505‐1.
  Tripathi, S., Misra, K., & Sanghvi, Y. S. (2005). Polymer supported carbodiimide strategy for the synthesis of N‐acylated derivatives of deoxy and ribo purinenucleosides using active esters. Bioorganic & Medicinal Chemistry Letters, 15, 5045–5048. doi: 10.1016/j.bmcl.2005.07.078.
  Tsunoda, H., Kudo, T., Ohkubo, A., Seio K., & Sekine, M. (2010). Synthesis of oligodeoxynucleotides using fully protected deoxynucleoside 3′‐phosphoramidite building blocks and base recognition of oligodeoxynucleotides incorporating N3‐cyano‐ethylthyamine. Molecules, 15, 7509–7531. doi: 10.3390/molecules15117509.
  Uchiyama, M., Aso, Y., & Noyori, R. (1993). O‐Selective phosphorylation of nucleosides without N‐protection. The Journal of Organic Chemistry, 58, 373–379. doi: 10.1021/jo00054a020.
  Umemoto, T., & Wada, T. (2005). Nitromethane as a scavenger of acrylonitrile in the deprotection of synthetic oligonucleotides. Tetrahedron Letters, 46, 4251–4253. doi: 10.1016/j.tetlet.2005.04.066.
  Urdea, M. S., Ku, L., Horn, T., Gee, Y. G., & Warner, B. D. (1986). Base modification and cloning efficiency of oligodeoxyribonucleotides synthesized by the phosphoramidite method: Methyl versus cyanoethyl phosphorous protection. Nucleic Acids Research Symposium Series, 16, 257–260.
  Uznanski, B., Grajkowski, A., & Wilk, A. (1989). The isopropoxyacetic group for convenient base protection during solid‐support synthesis of oligodeoxyribonucleotides and their triester analogs. Nucleic Acids Research, 17, 4863–4871. doi: 10.1093/nar/17.12.4863.
  Van Aerschot, A., Herdewijn, P., Janssen, G., & Vanderhaeghe, H. (1988). Protection of the lactam function of 2′‐deoxyinosine with a 2‐(4‐nitrophenyl)‐ethyl moiety. Nucleosides & Nucleotides, 7, 519–536. doi: 10.1080/07328318808075394.
  Vinayak, R., Anderson P., McCollum C., & Hampel, A. (1992). Chemical syntheis of RNA using fast oligonucleotide deprotection chemistry. Nucleic Acids Research, 20, 1265–1269. doi: 10.1093/nar/20.6.1265.
  Virta, P. (2009). Solid‐phase synthesis of base‐sensitive oligonucleotides. Arkivoc, iii, 54–83. doi: 10.3998/ark.5550190.0010.307.
  Vongsutilers, V., Daft, J. R., Shaughnessy, K. H., & Gannett, P. M. (2009). A general synthesis of C8‐arylpurine phosphoramidites. Molecules, 14, 3339–3352. doi: 10.3390/molecules14093339.
  Vu, H., McCollum, C., Jacobson, K., Theisen, P., Vinayak, R., Spiess, E., & Andrus, A. (1990). Fast oligonucleotide deprotection phosphoramidite chemistry for DNA synthesis. Tetrahedron Letters, 31, 7269‐7272 doi: 10.1016/S0040‐4039(00)88541‐X.
  Wada, T., Kobori, A., Kawahara, S., & Sekine, M. (1998). Synthesis and properties of oligodeoxyribonucleotides containing 4‐N‐acetylcytosine bases. Tetrahedron Letters, 38, 6907–6910. doi: 10.1016/S0040‐4039(98)01449‐X.
  Wagner, T., & Pfleiderer, W. (1997). Aglycone protection by the (2‐dansylethoxy)carbonyl ({= {2‐{[5‐(dimethylamino)naphthalen‐1‐yl] sulfonyl}ethoxy}carbonyl; dnseoc) group—A new variation in oligodeoxyribonucleotide synthesis. Helvetica Chimica Acta, 80, 200–212. doi: 10.1002/hlca.19970800118.
  Walbert, S., Pfleiderer, W., & Steiner, U. (2001). Photolabile protecting groups for nucleosides: Mechanistic studies of the 2‐(2‐nitrophenyl)ethyl group. Helvetica Chimica Acta, 84, 1601–1611. doi: 10.1002/1522‐2675(20010613)84:63.0.CO;2‐S.
  Waldmann, H., Heuser, A., & Reidel, A. (1994). Selective enzymic deprotection of hydroxy and amino groups in carbohydrates and nucleosides. Synlett, 1, 65–67. doi: 10.1055/s‐1994‐22740.
  Waldmann, H., & Reidel, A. (1997). The phenylacetyl group–The first amino protecting group that can be removed enzymatically from oligonucleotides in solution and on a solid support. Angewandte Chemie (International ed. in English, 36, 647–649. doi: 10.1002/anie.199706471.
  Waldmann, H., Reidel, A., Heuser, A., Meuhlegger, K., Von der Elt H., & Birkner, C. (1997). Nucleosides, nucleotides, and oligonucleotides containing enzymatically clevable protecting groups. USPT: 5677411.
  Watanabe, K. A., & Fox, J. J. (1966). A simple method for selective acylation of cytidine on the 4‐amino group. Angewandte Chemie (International ed. in English), 5, 579–580. doi: 10.1002/anie.196605792.
  Watkins, B. E., Kiely, J. S., & Rapoport, H. (1982). Synthesis of oligodeoxyribonucleotides using N‐(benzyloxycarbonyl)‐blocked nucleosides. Journal of the American Chemical Society, 104, 5702–5708. doi: 10.1021/ja00385a026.
  Weiler, J., & Hoheisel, J. D. (1996). Combining the prepartion of oligonucleotide arrays and synthesis of high‐quality primers. Analytical Chemistry, 243, 218–227. doi: 10.1006/abio.1996.0509.
  Welch, C. J., Bazin, H., Heikkilä, J., & Chattopadhyaya, J. (1985). Synthesis of C‐5 and N‐3 arenesulfenyl uridines. Preparation and properties of a new class of uracil protecting group. Acta Chemica Scandinavica, B39, 203–212. doi: 10.3891/acta.chem.scand.39b‐0203.
  Wiesler, W. T., & Caruthers, M. H. (1996) Synthesis of phosphorodithioate DNA via sulfur‐linked, base‐labile protecting groups. The Journal of Organic Chemistry, 61, 4272–4281. doi: 10.1021/jo960274y.
  Xu, J., Duffy, C. D., Chan, C. K. W., & Sutherland, J. D. (2014). Solid‐phase synthesis and hybrization behavior of partially 2′/3′ O acetylated RNA oligonucleotides. The Journal of Organic Chemistry, 79, 3311–3326. doi: org/10.1021/jo5002824.
  York, J. L. (1981). Effect of structure of the aglycon on the acid‐catalyzed hydrolysis of adenine nucleosides. The Journal of Organic Chemistry, 46, 2171–2173. doi: 10.1021/jo00323a040.
  Young, D. D., Edwards, W. F., Lusic, H., Lively, M. O., & Deiters, A. (2008). Light‐trigerred polymerase chain reaction. Chem Commun (Camb), 28, 462–464. doi: 10.1039/B715152G.
  Young, D. D., Lusic, H., Lively, M. O., & Deiters, A. (2009). Restriction enzyme‐free mutagenesis via the light regulation of DNA polymerization. Nucleic Acids Research, 37, e58. doi: 10.1093/nar/gkp150.
  Zhou, X.‐X., & Chattopadhyaya, J. (1986). Site‐specific modification of the pyrimidine residue during the deprotection of the fully‐protected diuridylic acid. Tetrahedron, 42, 5149–5156. doi: 10.1016/S0040‐4020(01)88067‐4.
  Zhou, X. X., Sandstr Öm, A., & Chattopadhyaya, J. (1986). A convenient preparation of 2‐N‐(4‐t‐butylbenzoyl)‐6‐O‐(2‐nitrophenyl)guanosine and its application in the synthesis of 5′ (GpGpGpU)3′ constituting the 3′‐anticodon stem of E.coli tRNAIle. Chemica Scripta, 26, 241–249.
  Zhu, X.‐F., Williams Jr., H. J., & Scott, A. I. (2003). An improved transient method for the synthesis of N‐benzoylated nucleosides. Synthetic Communications, 33, 1233–1243. doi: 10.1081/SCC‐120017200.
  Zoltewicz, J. A., & Clark, D. F. (1972). Kinetics and mechanism of the hydrolysis of guanosine and 7‐methylguanosine nucleosides in perchloric acid. The Journal of Organic Chemistry, 37, 1193–1197. doi: 10.1021/jo00973a025.
  Zoltewicz, J. A., Clark, D. F., Sharpless, T. W., & Grahe, G. (1970). Kinetics and mechanism of the hydrolysis of some purine nucleosides. Journal of the American Chemical Society, 92, 1741–1750. doi: 10.1021/ja00709a055.
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