Advertisement

Perspectives in Drug Discovery and Design

, Volume 4, Issue 1, pp 17–40 | Cite as

The chirality problem in P-substituted oligonucleotides

  • Alexandre V. Lebedev
  • Eric Wickstrom
Article

Summary

P-substituted oligonucleotides, which are oligonucleotide analogs where one (or more) bridging or nonbridging oxygen(s) of an internucleotide bond is substituted by another atom or group of atoms, are being studied as novel potential therapeutics. A chirality problem associated with the substitution of nonbridging oxygen is discussed. Synthesis, structure, hybridization and biological properties of the individual diastereomers of P-substituted oligonucleotides are reviewed.

Keywords

Oxygen Polymer Biological Property Potential Therapeutics Nonbridging Oxygen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cohen, J.S. (Ed.) Oligonucleotides: Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, FL, 1989.Google Scholar
  2. 2.
    Uhlmann, E. and Peyman, A., Chem. Rev., 90 (1990) 543.Google Scholar
  3. 3.
    Wickstrom, E. (Ed.) Prospects for Antisense Nucleic Acid Therapy of Cancer and AIDS, Wiley-Liss, New York, NY, 1991.Google Scholar
  4. 4.
    Murray, J.A.H. (Ed.) Antisense RNA and DNA, Wiley-Liss, New York, NY, 1992.Google Scholar
  5. 5.
    Crooke, S.T. and Lebleu, B. (Eds.) Antisense Research and Applications, CRC Press, Boca Raton, FL, 1993.Google Scholar
  6. 6.
    Knorre, D.G., Vlassov, V.V., Zarytova, V.F., Lebedev, A.V. and Fedorova, O.S., Design and Targeted Reactions of Oligonucleotide Derivatives, CRC Press, Boca Raton, FL, 1994.Google Scholar
  7. 7.
    Sanghvi, Y.S. and Cook, P.D. (Eds.) Carbohydrate Modifications in Antisense Research, ACS Symposium Series Vol. 580, American Chemical Society, Washington, DC, 1994.Google Scholar
  8. 8.
    Zon, G., Pharm. Res., 5 (1988) 539.Google Scholar
  9. 9.
    Thuong, N.T. and Hélène, C., Angew. Chem., Int. Ed. Engl., 32 (1993) 666.Google Scholar
  10. 10.
    Sarver, N., Cantin, E.M., Chang, P.S., Zaia, J.A., Ladne, P.A., Stephens, D.A. and Rossi, J.J., Science, 247 (1990) 1222.PubMedGoogle Scholar
  11. 11.
    Häuptle, M.T., Frank, R. and Dobberstein, B., Nucleic Acids Res., 14 (1986) 1427.Google Scholar
  12. 12.
    Minshull, J. and Hunt, T., Nucleic Acids Res., 14 (1986) 6433.Google Scholar
  13. 13.
    Cazenave, C., Loreau, N., Thuong, N.T., Toulmé, J.-J. and Hélène, C., Nucleic Acids Res., 15 (1987) 4717.Google Scholar
  14. 14.
    Egholm, M., Buchardt, O., Nielsen, P.E. and Berg, R.H., J. Am. Chem. Soc., 114 (1992) 1895.Google Scholar
  15. 15.
    Nielsen, P.E., Perspect. Drug Discov. Design, 4 (1996) 76.Google Scholar
  16. 16.
    Beaucage, S.L. and Iyer, R., Tetrahedron, 49 (1993) 6123.Google Scholar
  17. 17.
    Gryaznov, S.M. and Chen, J.-K., J. Am. Chem. Soc., 116 (1994) 3143.Google Scholar
  18. 18.
    Gryaznov, S.M., Lloyd, D.H., Chen, J.-K., Schultz, R.G., DeDionisio, L.A., Ratmeyer, L. and Wilson, W.D., Proc. Natl. Acad. Sci. USA, 92 (1995) 5798.Google Scholar
  19. 19.
    Reynolds, M.A., Schwartz, D.A., Riley, T.A., Vaghefi, M.M., Hogrefe, R.I., Jaeger, J.A., Lebedev, A.V. and Arnold Jr., L.J., First International Antisense Conference of Japan, Kyoto, December 4–7, 1994, Abstract P1-06.Google Scholar
  20. 20.
    Miller, P.S., Yano, J., Yano, E., Carroll, C., Jayaraman, K. and Ts'o, P.O.P., Biochemistry, 18 (1979) 5134.Google Scholar
  21. 21.
    Engels, J. and Jäger, A., Angew. Chem., Int. Ed. Engl., 21 (1982) 912.Google Scholar
  22. 22.
    Eckstein, F., Angew. Chem., Int. Ed. Engl., 22 (1983) 423.Google Scholar
  23. 23.
    Burgers, P.M.J. and Eckstein, F., Biochemistry, 18 (1978) 592.Google Scholar
  24. 24.
    Miller, P.S., Fang, K.N., Kondo, N.S. and Ts'o, P.O.P., J. Am. Chem. Soc., 93 (1971) 6657.Google Scholar
  25. 25.
    Jensen, D.E. and Reed, D.J., Biochemistry, 17 (1978) 5098.Google Scholar
  26. 26.
    Stec, W.J., Zon, G. and Uznanski, B., J. Chromatogr., 326 (1985) 263.Google Scholar
  27. 27.
    Reitz, G. and Pfleiderer, W., Chem. Ber., 108 (1975) 2878.Google Scholar
  28. 28.
    Lebedev, A.V. and Rezvukhin, A.I., Izv. Sib. Otd. Acad. Nauk USSR, Ser. Khim. Nauk, 2 (1975) 149.Google Scholar
  29. 29.
    Ozaki, H., Yamana, K. and Shimidzu, T., Tetrahedron Lett., 30 (1989) 5899.Google Scholar
  30. 30.
    Froehler, B., Ng, P. and Matteucci, M., Nucleic Acids Res., 16 (1988) 4831.Google Scholar
  31. 31.
    Letsinger, R.L., Bach, S.A. and Eadie, J.S., Nucleic Acids Res., 14 (1986) 3487.Google Scholar
  32. 32.
    Lesnikowski, Z.J., Bioorg. Chem., 21 (1993) 127.Google Scholar
  33. 33.
    Stec, W.J. and Wilk, A., Angew. Chem., Int. Ed. Engl., 33 (1994) 709.Google Scholar
  34. 34.
    Knorre, D.G., Lebedev, A.V., Levina, A.S., Rezvukhin, A.I. and Zarytova, V.F., Tetrahedron, 30 (1974) 3073.Google Scholar
  35. 35.
    Werstiuk, E.S. and Neilson, T., Can. J. Chem., 50 (1972) 1283.Google Scholar
  36. 36.
    Kan, L.S., Cheng, D.M., Miller, P.S., Yano, J. and Ts'o, P.O.P., Biochemistry, 19 (1980) 2122.Google Scholar
  37. 37.
    Vyazovkina, E.V., Komarova, N.I. and Lebedev, A.V., Bioorg. Khim., 19 (1993) 86.Google Scholar
  38. 38.
    Vyazovkina, E.V., Rife, J.P., Lebedev, A.V. and Wickstrom, E., Nucleic Acids Res., 21 (1993) 5957.Google Scholar
  39. 39.
    Murakami, A., Tamura, Y., Wada, H. and Makino, K., Anal. Biochem., 223 (1994) 285.Google Scholar
  40. 40.
    Wilk, A. and Stec, W.J., Nucleic Acids Res., 23 (1995) 530.Google Scholar
  41. 41.
    Zon, G., J. Protein Chem., 6 (1987) 131.Google Scholar
  42. 42.
    LaPlanche, L., James, T.L., Powell, C., Wilson, D.W., Uznanski, B., Stec, W.J., Summers, M.F. and Zon, G., Nucleic Acids Res., 14 (1986) 9081.Google Scholar
  43. 43.
    Stec, W.J. and Zon, G., Tetrahedron Lett., 25 (1984) 5275.Google Scholar
  44. 44.
    Hayakawa, Y., Hirose, M., Hayakawa, M. and Noyori, R., J. Org. Chem., 60 (1995) 925.Google Scholar
  45. 45.
    Karpova, G.G., Kozlova, O.O. and Pichko, N.P., Izv. Sib. Otd. Acad. Nauk USSR, Ser. Khim. Nauk, 7 (1983) 96.Google Scholar
  46. 46.
    Vtorushina, I.A., Gorbunov, Yu.A., Zarytova, V.F., Komarova, N.I., Lebedev, A.V., Lokhov, S.G., Manajenko, A.V., Siniakov, A.N. and Shishkina, I.G., Bioorg. Khim., 18 (1992) 92.Google Scholar
  47. 47.
    Zarytova, V.F. and Shishkina, I.G., Anal. Biochem., 188 (1990) 214.Google Scholar
  48. 48.
    Vyazovkina, E.V., Savchenko, E.V., Lokhov, S.G., Engels, J.W., Wickstrom, E. and Lebedev, A.V., Nucleic Acids Res., 22 (1994) 2404.Google Scholar
  49. 49.
    Pless, R.C. and Ts'o, P.O.P., Biochemistry, 16 (1977) 1239.Google Scholar
  50. 50.
    Miller, P.S., Dreon, N., Pulford, S.M. and McParland, K.B., J. Biol. Chem., 255 (1980) 9659.Google Scholar
  51. 51.
    Fathi, R., Huang, Q., Coppola, G., Delaney, W., Teasdale, R., Kreig, A.M. and Cook, A.F., Nucleic Acids Res., 22 (1994) 5416.Google Scholar
  52. 52.
    Cook, A.F., Fathi, R., Huang, Q., Coppola, G., Delaney, W. and Syi, J.-L., Nucleos. Nucleot., 14 (1995) 1005.Google Scholar
  53. 53.
    Abramova, T.V., Vorobyov, Yu.N. and Lebedev, A.V., Bioorg. Khim., 12 (1986) 1335.Google Scholar
  54. 54.
    Taylor, J.W., Schmidt, W., Cosstick, R., Okruszek, A. and Eckstein, F., Nucleic Acids Res., 13 (1985) 8749.Google Scholar
  55. 55.
    Kitamura, M., Ozaki, H., Yamana, K. and Shimidzu, T., Nucleos. Nucleot., 11 (1992) 473.Google Scholar
  56. 56.
    Lesnikowski, Z.J., Jaworska, M. and Stec, W.J., Nucleic Acids Res., 18 (1990) 2109.Google Scholar
  57. 57.
    Lebedev, A.V., Wenzinger, G.R. and Wickstrom, E., Tetrahedron Lett., 31 (1990) 851.Google Scholar
  58. 58.
    Löschner, T. and Engels, J., Tetrahedron Lett., 30 (1989) 5587.Google Scholar
  59. 59.
    Rozmanitz, P., Eisenhardt, S., Bats, J.W. and Engels, J.W., Tetrahedron, 50 (1994) 5719.Google Scholar
  60. 60.
    Fujii, M., Ozaki, K., Sekine, M. and Hata, T., Tetrahedron, 43 (1987) 3395.Google Scholar
  61. 61.
    Almer, H., Stawinski, J., Stromberg, R. and Thelin, M., J. Org. Chem., 57 (1992) 6163.Google Scholar
  62. 62.
    Stawinski, J., Stromberg, R. and Thelin, M., Nucleos. Nucleot., 10 (1991) 511.Google Scholar
  63. 63.
    Almer, H., Stawinski, J. and Stromberg, R., Nucleos. Nucleot., 14 (1995) 879.Google Scholar
  64. 64.
    Seela, F. and Kretschmer, U., Nucleos. Nucleot., 10 (1991) 711.Google Scholar
  65. 65.
    Almer, H., Stawinski, J. and Stromberg, R., J. Chem. Soc., Chem. Commun., (1994) 1459.Google Scholar
  66. 66.
    Battistini, C., Brasca, M.G. and Fustinoni, S., Nucleos. Nucleot., 10 (1991) 723.Google Scholar
  67. 67.
    Battistini, C., Brasca, M.G., Fustinoni, S. and Lazzari, E., Tetrahedron, 48 (1992) 3209.Google Scholar
  68. 68.
    Ohtsuka, E., Shiraishi, M. and Ikehara, M., Tetrahedron, 41 (1985) 5271.Google Scholar
  69. 69.
    Cosstick, R. and Williams, D.M., Nucleic Acids Res., 15 (1987) 9921.Google Scholar
  70. 70.
    Knorre, D.G., Zarytova, V.F., Lebedev, A.V., Khalimskaya, L.M. and Sheshegova, E.A., Nucleic Acids Res., 5 (1978) 1253.Google Scholar
  71. 71.
    Wang, C.G., Wang, L.X., Yang, X.B., Jiang, T.Y. and Zhang, L.H., Nucleic Acids Res., 21 (1993) 3245.Google Scholar
  72. 72.
    Marugg, J.E., De Vroom, E., Dreef, C.E., Tromp, M., Van der Marel, G.A. and Van Boom, J.H., Nucleic Acids Res., 14 (1986) 2171.Google Scholar
  73. 73.
    Lesnikowski, Z.J. and Shibinska, A., Tetrahedron, 42 (1986) 5025.Google Scholar
  74. 74.
    Lesnikowski, Z.J. and Jaworska, M.M., Tetrahedron Lett., 30 (1989) 3821.Google Scholar
  75. 75.
    Lesnikowski, Z.J., Nucleos. Nucleot., 11 (1992) 1621.Google Scholar
  76. 76.
    Lesnikowski, Z.J., Wolkanin, P.J. and Setc, W.J., Tetrahedron Lett., 28 (1987) 5535.Google Scholar
  77. 77.
    Lesnikowski, Z.J., Jaworska, M.M. and Stec, W.J., Nucleic Acids Res., 16 (1988) 11675.Google Scholar
  78. 78.
    Lesnikowski, Z.J., Jaworska-Maslanka, M.M. and Stec, W.J., Nucleos. Nucleot., 10 (1991) 733.Google Scholar
  79. 79.
    Hayakawa, Y., Uchiyama, N. and Noyori, R., Tetrahedron Lett., 25 (1984) 4003.Google Scholar
  80. 80.
    Cormier, J.F. and Pannunzio, T., Tetrahedron Lett., 32 (1991) 7161.Google Scholar
  81. 81.
    Lebedev, A.V., Rife, J.P., Seligsohn, H.W., Wenzinger, G.R. and Wickstrom, E., Tetrahedron Lett., 31 (1990) 855.Google Scholar
  82. 82.
    Wozniak, L.A., Pyzowski, J., Wieczorek, M. and Stec, W.J., J. Org. Chem., 59 (1994) 5843.Google Scholar
  83. 83.
    Le Bec, C. and Wickstrom, E., Tetrahedron Lett., 35 (1994) 9525.Google Scholar
  84. 84.
    Le Bec, C. and Wickstrom, E., J. Org. Chem., 61 (1996) in press.Google Scholar
  85. 85.
    Stec, W.J., Grajkowski, A., Koziolkiewicz, M. and Uznanski, B., Nucleic Acids Res., 19 (1991) 5883.Google Scholar
  86. 86.
    Koziolkiewicz, M., Krakowiak, A., Kwinkowski, M., Boczkowska, M. and Stec, W.J., Nucleic Acids Res., manuscript submitted for publication.Google Scholar
  87. 87.
    Matsura, H. and Eckstein, F., Eur. J. Biochem., 3 (1968) 448.Google Scholar
  88. 88.
    Eckstein, F. and Gindl, H., Eur. J. Biochem., 13 (1970) 558.Google Scholar
  89. 89.
    Hacia, J.G., Wold, B.J. and Dervan, P.B., Biochemistry, 33 (1994) 5367.Google Scholar
  90. 90.
    Tang, J., Roskey, A., Li, Y. and Agrawal, S., Nucleos. Nucleot., 14 (1995) 985.Google Scholar
  91. 91.
    Higuchi, H., Endo, T. and Kaji, A., Biochemistry, 29 (1990) 8747.Google Scholar
  92. 92.
    Victorova, L.S., Dyatkina, N.B., Mozzherin, D.Yu., Atrazhev, A.M., Krayevsky, A.A. and Kukhanova, M.K., Nucleic Acids Res., 20 (1992) 783.Google Scholar
  93. 93.
    Chacko, K.K., Linder, K., Saenger, W. and Miller, P.S., Nucleic Acids Res., 27 (1983) 2801.Google Scholar
  94. 94.
    Han, F., Watt, W., Duchamp, D.J., Callahan, L., Kezdy, F.J. and Agarwal, K., Nucleic Acids Res., 18 (1990) 2759.Google Scholar
  95. 95.
    Bentrude, W.G., Sopchik, A.E., Bajwa, G.S., Setzer, W.N. and Sheldrick, W.S., Acta Crystallogr.; C42 (1986) 1027.Google Scholar
  96. 96.
    Szabo, T., Noreus, D., Norrestam, R. and Stawinski, J., Nucleic Acids Res., 21 (1993) 3921.Google Scholar
  97. 97.
    Bower, M., Summers, M.F., Powell, C., Shinozuka, K., Regan, J.B., Zon, G. and Wilson, W.D., Nucleic Acids Res., 15 (1987) 4915.Google Scholar
  98. 98.
    Summers, M.F., Powell, C., Egan, W., Byrd, A., Wilson, W.D. and Zon, G., Nucleic Acids Res., 14 (1986) 7421.Google Scholar
  99. 99.
    Löschner, T. and Engels, J.W., Nucleic Acids Res., 18 (1990) 5083.Google Scholar
  100. 100.
    Bothner-By, A.A., Stephens, R.L., Lee, J., Warren, C.D. and Jeanloz, R.W., J. Am. Chem. Soc., 106 (1984) 811.Google Scholar
  101. 101.
    Vyazovkina, E.V., Engels, J.W. and Lebedev, A.V., Bioorg. Khim., 19 (1993) 197.Google Scholar
  102. 102.
    Lebedev, A.V., Frauendorf, A., Vyazovkina, E.V. and Engels, J.W., Tetrahedron, 49 (1993) 1042.Google Scholar
  103. 103.
    Koziolkiewicz, M., Uznanski, B., Stec, W.J. and Zon, G., Chem. Scripta, 26 (1986) 251.Google Scholar
  104. 104.
    Guga, P.A., Koziolkiewicz, M., Okruszek, A., Uznanski, B. and Stec, W.J., Nucleos. Nucleot., 6 (1987) 111.Google Scholar
  105. 105.
    Abramova, T.V., Komarova, N.I., Lebedev, A.V. and Tagay, S.A., Bioorg. Khim., 10 (1984) 1366.Google Scholar
  106. 106.
    Stawinski, J. and Thelin, M., J. Org. Chem., 59 (1994) 130.Google Scholar
  107. 107.
    Stec, W.J., Zon, G., Egan, W. and Stec, B., J. Am. Chem. Soc., 106 (1984) 6077.Google Scholar
  108. 108.
    Potter, B.V.L., Connolly, B.A. and Eckstein, F., Biochemistry, 22 (1983) 1369.Google Scholar
  109. 109.
    Potter, B.V.L., Romaniuk, P.J. and Eckstein, F., J. Biol. Chem., 258 (1983) 1758.Google Scholar
  110. 110.
    Bryant, R.F. and Benkovic, S.J., Biochemistry, 18 (1979) 2825.Google Scholar
  111. 111.
    Burgers, P.M.J. and Eckstein, F., Proc. Natl. Acad. Sci. USA, 75 (1978) 4798.Google Scholar
  112. 112.
    Koziolkiewicz, M. and Wilk, A., In Agrawal, S. (Ed.) Methods in Molecular Biology, Vol. 20: Protocols for Oligonucleotides and their Analogs, Synthesis and Properties, Humana Press, Totowa, NJ, 1993, pp. 207–224.Google Scholar
  113. 113.
    Ferguson, D.M. and Kollman, P.A., Antisense Res. Dev., 1 (1991) 243.Google Scholar
  114. 114.
    Durand, M., Maurizot, J.C., Asseline, U., Barbier, C., Thuong, N.T. and Hélène, C., Nucleic Acids Res., 17 (1989) 1823.Google Scholar
  115. 115.
    Abramova, T.V., Vorobyov, Yu.N. and Lebedev, A.V., Bioorg. Khim., 12 (1986) 1335.Google Scholar
  116. 116.
    Vorobyov, Yu.N., Molekularnaya Biol., 24 (1990) 58.Google Scholar
  117. 117.
    Hausheer, F.H., Singh, U.C., Palmer, T.C. and Saxe, J.D., J. Am. Chem. Soc., 112 (1990) 9468.Google Scholar
  118. 118.
    Hausheer, F.H., Singh, U.C., Saxe, J.D., Colvin, O.M. and Ts'o, P.O.P., Anti-Cancer Drug Des., 5 (1990) 159.Google Scholar
  119. 119.
    Hausheer, F.H., Rao, B.G., Saxe, J.D. and Singh, U.C., J. Am. Chem. Soc., 114 (1992) 3201.Google Scholar
  120. 120.
    Swarnalatha, Y. and Yathindra, N., J. Biomol. Struct. Dyn., 10 (1993) 1023.Google Scholar
  121. 121.
    Kibler-Herzog, L., Kell, B., Zon, G., Shinozuka, K., Mizan, S. and Wilson, W.D., Nucleic Acids Res., 18 (1990) 3545.Google Scholar
  122. 122.
    Jaroszewski, J.W., Syi, J.-J., Maizel, J. and Cohen, J.S., Anti-Cancer Drug Des., 7 (1992) 253.Google Scholar
  123. 123.
    Miller, P.S., Annan, N.D., McParland, K.B. and Pulford, S.M., Biochemistry, 21 (1982) 2507.Google Scholar
  124. 124.
    Arnold Jr., L., First International Antisense Conference of Japan, Kyoto, December 4–7, 1994, Abstract OP-31.Google Scholar
  125. 125.
    Noble, S.A., Fisher, E.F. and Caruthers, M.H., Nucleic Acids Res., 12 (1984) 3387.Google Scholar
  126. 126.
    Gallo, K.A., Shao, K.-L., Phillips, L.R., Regan, J.B., Koziolkiewicz, M., Uznanski, B., Stec, W.J. and Zon, G., Nucleic Acids Res., 14 (1986) 7405.Google Scholar
  127. 127.
    Charubala, R., Pfleiderer, W., Suhadolnik, R.J. and Sobol, R.W., Nucleos. Nucleot., 10 (1991) 383.Google Scholar
  128. 128.
    Abramova, T.V., Vlassov, V.V., Lebedev, A.V. and Ryte, A.S., FEBS Lett., 236 (1988) 243.Google Scholar
  129. 129.
    Abramova, T.V., Lebedev, A.V. and Ryte, A.S., Molekularnaya Biol., 22 (1988) 1285.Google Scholar
  130. 130.
    Abramova, T.V., Knorre, D.G., Lebedev, A.V., Pichko, N.P. and Fedorova, O.S., Bioorg. Khim., 11 (1985) 1642.Google Scholar
  131. 131.
    Cazenave, C., Stein, C.A., Loreau, N., Thuong, N.T., Neckers, L.M., Subasinghe, C., Hélène, C., Cohen, J.S. and Toulmé, J.-J., Nucleic Acids Res., 17 (1989) 4255.PubMedGoogle Scholar

Copyright information

© ESCOM Science Publishers B.V. 1996

Authors and Affiliations

  • Alexandre V. Lebedev
    • 1
  • Eric Wickstrom
    • 2
  1. 1.Genta, Inc.San DiegoUSA
  2. 2.Department of PharmacologyThomas Jefferson UniversityPhiladelphiaUSA

Personalised recommendations