Synthesis of RNA Bearing C5-polyamine Modified Pyrimidine Nucleosides at the 3´-end by T4 RNA Ligase

Author(s): Tomokazu Masuda , Shingo Kimura , Mohammad Mehedi Masud , Hiroaki Ozaki* .

Journal Name: Letters in Organic Chemistry

Volume 16 , Issue 2 , 2019

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Abstract:

The incorporation of the modified nucleoside into the 3´-overhang regions of short interfering RNAs (siRNAs) has been reported to enhance their nuclease resistance and improve RNA interference activity. In this study, DNA 2-mers containing C5-polyamine-modified pyrimidine nucleosides were synthesized and then ligated to the 3´-end of the RNA by T4 RNA ligase. The modification of the base moiety with tris(2-aminoethyl)amine affected the ligation efficiency, but the DNA 2-mer containing only one modified nucleoside was ligated with sufficient efficiency. We propose a novel synthetic route to modified siRNA bearing various modified groups in the 3´-overhang region.

Keywords: C5-modified pyrimidine, siRNA, T4 RNA Ligase, tris(2-aminoethyl)amine, oligonucleotides, genes.

[1]
Kurreck, J. Eur. J. Biochem., 2003, 270, 1628-1644.
[2]
Monia, B.P.; Lesnik, E.A.; Gonzales, C.; Lima, W.F.; McGee, D.; Guinosso, C.J.; Kawasaki, A.M.; Cook, P.D.; Freier, S.M. J. Biol. Chem., 1993, 268, 14514-14522.
[3]
Elbashir, S.M.; Harborth, J.; Lendeckel, W.; Yalcin, A.; Weber, K.; Tuschl, T. Nature, 2001, 411, 494-498.
[4]
Ueno, Y.; Watanabe, Y.; Shibata, A.; Yoshikawa, K.; Takano, T.; Kohara, M.; Kitade, Y. Bioorg. Med. Chem., 2009, 17, 1974-1981.
[5]
Xu, L.; Wang, X.; He, H.; Zhou, J.; Li, X.; Ma, H.; Li, Z.; Zeng, Y.; Shao, R.; Cen, S.; Wang, Y. Biochemistry, 2015, 54, 1268-1277.
[6]
Maniataki, E.; Mourelatos, Z. Genes Dev., 2005, 19, 2979-2990.
[7]
Khvorova, A.; Reynolds, A.; Jayasena, S.D. Cell, 2003, 115, 209-216.
[8]
Schwarz, D.S.; Hutvagner, G.; Du, T.; Xu, Z.; Aronin, N.; Zamore, P.D. Cell, 2003, 115, 199-208.
[9]
Bramsen, J.B.; Laursen, M.B.; Nielsen, A.F.; Hansen, T.B.; Bus, C.; Langkjær, N.; Babu, B.R.; Højland, T.; Abramov, M.; Van Aerschot, A.; Odadzic, D.; Smicius, R.; Haas, J.; Andree, C.; Barman, J.; Wenska, M.; Srivastava, P.; Zhou, C.; Honcharenko, D.; Hess, S.; Müller, E.; V , Bobkov. G.; Mikhailov, S.N.; Fava, E.; Meyer, T.F.; Chattopadhyaya, J.; Zerial, M.; Engels, J.W.; Herdewijn, P.; Wengel, J.; Kjems, J. Nucleic Acids Res., 2009, 37, 2867-2881.
[10]
Masud, M.M.; Masuda, T.; Inoue, Y.; Kuwahara, M.; Sawai, H.; Ozaki, H. Bioorg. Med. Chem. Lett., 2011, 21, 715-717.
[11]
Silber, R.; Malathi, V.G.; Hurwitz, J. Proc. Natl. Acad. Sci. USA, 1972, 69, 3009-3013.
[12]
Cranston, J.W.; Silber, R.; Malathi, V.G.; Hurwitz, J. J. Biol. Chem., 1974, 249, 7447-7456.
[13]
Sugino, A.; Snoper, T.J.; Cozzarelli, N.R. J. Biol. Chem., 1977, 252, 1732-1738.
[14]
Richardson, R.W.; Gumport, R.I. Nucleic Acids Res., 1983, 11, 6167-6184.
[15]
Cosstick, R.; McLaughlin, L.W.; Eckstein, F. Nucleic Acids Res., 1984, 12, 1791-1810.
[16]
Kore, R.A.; Charles, I.; Yang, L.; Kuersten, S. Nucleosides Nucleotides Nucleic Acids, 2009, 28, 292-302.


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Article Details

VOLUME: 16
ISSUE: 2
Year: 2019
Page: [122 - 127]
Pages: 6
DOI: 10.2174/1570178615666180910111359
Price: $58

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