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.
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References
Cohen, J.S. (Ed.) Oligonucleotides: Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, FL, 1989.
Uhlmann, E. and Peyman, A., Chem. Rev., 90 (1990) 543.
Wickstrom, E. (Ed.) Prospects for Antisense Nucleic Acid Therapy of Cancer and AIDS, Wiley-Liss, New York, NY, 1991.
Murray, J.A.H. (Ed.) Antisense RNA and DNA, Wiley-Liss, New York, NY, 1992.
Crooke, S.T. and Lebleu, B. (Eds.) Antisense Research and Applications, CRC Press, Boca Raton, FL, 1993.
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.
Sanghvi, Y.S. and Cook, P.D. (Eds.) Carbohydrate Modifications in Antisense Research, ACS Symposium Series Vol. 580, American Chemical Society, Washington, DC, 1994.
Zon, G., Pharm. Res., 5 (1988) 539.
Thuong, N.T. and Hélène, C., Angew. Chem., Int. Ed. Engl., 32 (1993) 666.
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.
Häuptle, M.T., Frank, R. and Dobberstein, B., Nucleic Acids Res., 14 (1986) 1427.
Minshull, J. and Hunt, T., Nucleic Acids Res., 14 (1986) 6433.
Cazenave, C., Loreau, N., Thuong, N.T., Toulmé, J.-J. and Hélène, C., Nucleic Acids Res., 15 (1987) 4717.
Egholm, M., Buchardt, O., Nielsen, P.E. and Berg, R.H., J. Am. Chem. Soc., 114 (1992) 1895.
Nielsen, P.E., Perspect. Drug Discov. Design, 4 (1996) 76.
Beaucage, S.L. and Iyer, R., Tetrahedron, 49 (1993) 6123.
Gryaznov, S.M. and Chen, J.-K., J. Am. Chem. Soc., 116 (1994) 3143.
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.
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.
Miller, P.S., Yano, J., Yano, E., Carroll, C., Jayaraman, K. and Ts'o, P.O.P., Biochemistry, 18 (1979) 5134.
Engels, J. and Jäger, A., Angew. Chem., Int. Ed. Engl., 21 (1982) 912.
Eckstein, F., Angew. Chem., Int. Ed. Engl., 22 (1983) 423.
Burgers, P.M.J. and Eckstein, F., Biochemistry, 18 (1978) 592.
Miller, P.S., Fang, K.N., Kondo, N.S. and Ts'o, P.O.P., J. Am. Chem. Soc., 93 (1971) 6657.
Jensen, D.E. and Reed, D.J., Biochemistry, 17 (1978) 5098.
Stec, W.J., Zon, G. and Uznanski, B., J. Chromatogr., 326 (1985) 263.
Reitz, G. and Pfleiderer, W., Chem. Ber., 108 (1975) 2878.
Lebedev, A.V. and Rezvukhin, A.I., Izv. Sib. Otd. Acad. Nauk USSR, Ser. Khim. Nauk, 2 (1975) 149.
Ozaki, H., Yamana, K. and Shimidzu, T., Tetrahedron Lett., 30 (1989) 5899.
Froehler, B., Ng, P. and Matteucci, M., Nucleic Acids Res., 16 (1988) 4831.
Letsinger, R.L., Bach, S.A. and Eadie, J.S., Nucleic Acids Res., 14 (1986) 3487.
Lesnikowski, Z.J., Bioorg. Chem., 21 (1993) 127.
Stec, W.J. and Wilk, A., Angew. Chem., Int. Ed. Engl., 33 (1994) 709.
Knorre, D.G., Lebedev, A.V., Levina, A.S., Rezvukhin, A.I. and Zarytova, V.F., Tetrahedron, 30 (1974) 3073.
Werstiuk, E.S. and Neilson, T., Can. J. Chem., 50 (1972) 1283.
Kan, L.S., Cheng, D.M., Miller, P.S., Yano, J. and Ts'o, P.O.P., Biochemistry, 19 (1980) 2122.
Vyazovkina, E.V., Komarova, N.I. and Lebedev, A.V., Bioorg. Khim., 19 (1993) 86.
Vyazovkina, E.V., Rife, J.P., Lebedev, A.V. and Wickstrom, E., Nucleic Acids Res., 21 (1993) 5957.
Murakami, A., Tamura, Y., Wada, H. and Makino, K., Anal. Biochem., 223 (1994) 285.
Wilk, A. and Stec, W.J., Nucleic Acids Res., 23 (1995) 530.
Zon, G., J. Protein Chem., 6 (1987) 131.
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.
Stec, W.J. and Zon, G., Tetrahedron Lett., 25 (1984) 5275.
Hayakawa, Y., Hirose, M., Hayakawa, M. and Noyori, R., J. Org. Chem., 60 (1995) 925.
Karpova, G.G., Kozlova, O.O. and Pichko, N.P., Izv. Sib. Otd. Acad. Nauk USSR, Ser. Khim. Nauk, 7 (1983) 96.
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.
Zarytova, V.F. and Shishkina, I.G., Anal. Biochem., 188 (1990) 214.
Vyazovkina, E.V., Savchenko, E.V., Lokhov, S.G., Engels, J.W., Wickstrom, E. and Lebedev, A.V., Nucleic Acids Res., 22 (1994) 2404.
Pless, R.C. and Ts'o, P.O.P., Biochemistry, 16 (1977) 1239.
Miller, P.S., Dreon, N., Pulford, S.M. and McParland, K.B., J. Biol. Chem., 255 (1980) 9659.
Fathi, R., Huang, Q., Coppola, G., Delaney, W., Teasdale, R., Kreig, A.M. and Cook, A.F., Nucleic Acids Res., 22 (1994) 5416.
Cook, A.F., Fathi, R., Huang, Q., Coppola, G., Delaney, W. and Syi, J.-L., Nucleos. Nucleot., 14 (1995) 1005.
Abramova, T.V., Vorobyov, Yu.N. and Lebedev, A.V., Bioorg. Khim., 12 (1986) 1335.
Taylor, J.W., Schmidt, W., Cosstick, R., Okruszek, A. and Eckstein, F., Nucleic Acids Res., 13 (1985) 8749.
Kitamura, M., Ozaki, H., Yamana, K. and Shimidzu, T., Nucleos. Nucleot., 11 (1992) 473.
Lesnikowski, Z.J., Jaworska, M. and Stec, W.J., Nucleic Acids Res., 18 (1990) 2109.
Lebedev, A.V., Wenzinger, G.R. and Wickstrom, E., Tetrahedron Lett., 31 (1990) 851.
Löschner, T. and Engels, J., Tetrahedron Lett., 30 (1989) 5587.
Rozmanitz, P., Eisenhardt, S., Bats, J.W. and Engels, J.W., Tetrahedron, 50 (1994) 5719.
Fujii, M., Ozaki, K., Sekine, M. and Hata, T., Tetrahedron, 43 (1987) 3395.
Almer, H., Stawinski, J., Stromberg, R. and Thelin, M., J. Org. Chem., 57 (1992) 6163.
Stawinski, J., Stromberg, R. and Thelin, M., Nucleos. Nucleot., 10 (1991) 511.
Almer, H., Stawinski, J. and Stromberg, R., Nucleos. Nucleot., 14 (1995) 879.
Seela, F. and Kretschmer, U., Nucleos. Nucleot., 10 (1991) 711.
Almer, H., Stawinski, J. and Stromberg, R., J. Chem. Soc., Chem. Commun., (1994) 1459.
Battistini, C., Brasca, M.G. and Fustinoni, S., Nucleos. Nucleot., 10 (1991) 723.
Battistini, C., Brasca, M.G., Fustinoni, S. and Lazzari, E., Tetrahedron, 48 (1992) 3209.
Ohtsuka, E., Shiraishi, M. and Ikehara, M., Tetrahedron, 41 (1985) 5271.
Cosstick, R. and Williams, D.M., Nucleic Acids Res., 15 (1987) 9921.
Knorre, D.G., Zarytova, V.F., Lebedev, A.V., Khalimskaya, L.M. and Sheshegova, E.A., Nucleic Acids Res., 5 (1978) 1253.
Wang, C.G., Wang, L.X., Yang, X.B., Jiang, T.Y. and Zhang, L.H., Nucleic Acids Res., 21 (1993) 3245.
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.
Lesnikowski, Z.J. and Shibinska, A., Tetrahedron, 42 (1986) 5025.
Lesnikowski, Z.J. and Jaworska, M.M., Tetrahedron Lett., 30 (1989) 3821.
Lesnikowski, Z.J., Nucleos. Nucleot., 11 (1992) 1621.
Lesnikowski, Z.J., Wolkanin, P.J. and Setc, W.J., Tetrahedron Lett., 28 (1987) 5535.
Lesnikowski, Z.J., Jaworska, M.M. and Stec, W.J., Nucleic Acids Res., 16 (1988) 11675.
Lesnikowski, Z.J., Jaworska-Maslanka, M.M. and Stec, W.J., Nucleos. Nucleot., 10 (1991) 733.
Hayakawa, Y., Uchiyama, N. and Noyori, R., Tetrahedron Lett., 25 (1984) 4003.
Cormier, J.F. and Pannunzio, T., Tetrahedron Lett., 32 (1991) 7161.
Lebedev, A.V., Rife, J.P., Seligsohn, H.W., Wenzinger, G.R. and Wickstrom, E., Tetrahedron Lett., 31 (1990) 855.
Wozniak, L.A., Pyzowski, J., Wieczorek, M. and Stec, W.J., J. Org. Chem., 59 (1994) 5843.
Le Bec, C. and Wickstrom, E., Tetrahedron Lett., 35 (1994) 9525.
Le Bec, C. and Wickstrom, E., J. Org. Chem., 61 (1996) in press.
Stec, W.J., Grajkowski, A., Koziolkiewicz, M. and Uznanski, B., Nucleic Acids Res., 19 (1991) 5883.
Koziolkiewicz, M., Krakowiak, A., Kwinkowski, M., Boczkowska, M. and Stec, W.J., Nucleic Acids Res., manuscript submitted for publication.
Matsura, H. and Eckstein, F., Eur. J. Biochem., 3 (1968) 448.
Eckstein, F. and Gindl, H., Eur. J. Biochem., 13 (1970) 558.
Hacia, J.G., Wold, B.J. and Dervan, P.B., Biochemistry, 33 (1994) 5367.
Tang, J., Roskey, A., Li, Y. and Agrawal, S., Nucleos. Nucleot., 14 (1995) 985.
Higuchi, H., Endo, T. and Kaji, A., Biochemistry, 29 (1990) 8747.
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.
Chacko, K.K., Linder, K., Saenger, W. and Miller, P.S., Nucleic Acids Res., 27 (1983) 2801.
Han, F., Watt, W., Duchamp, D.J., Callahan, L., Kezdy, F.J. and Agarwal, K., Nucleic Acids Res., 18 (1990) 2759.
Bentrude, W.G., Sopchik, A.E., Bajwa, G.S., Setzer, W.N. and Sheldrick, W.S., Acta Crystallogr.; C42 (1986) 1027.
Szabo, T., Noreus, D., Norrestam, R. and Stawinski, J., Nucleic Acids Res., 21 (1993) 3921.
Bower, M., Summers, M.F., Powell, C., Shinozuka, K., Regan, J.B., Zon, G. and Wilson, W.D., Nucleic Acids Res., 15 (1987) 4915.
Summers, M.F., Powell, C., Egan, W., Byrd, A., Wilson, W.D. and Zon, G., Nucleic Acids Res., 14 (1986) 7421.
Löschner, T. and Engels, J.W., Nucleic Acids Res., 18 (1990) 5083.
Bothner-By, A.A., Stephens, R.L., Lee, J., Warren, C.D. and Jeanloz, R.W., J. Am. Chem. Soc., 106 (1984) 811.
Vyazovkina, E.V., Engels, J.W. and Lebedev, A.V., Bioorg. Khim., 19 (1993) 197.
Lebedev, A.V., Frauendorf, A., Vyazovkina, E.V. and Engels, J.W., Tetrahedron, 49 (1993) 1042.
Koziolkiewicz, M., Uznanski, B., Stec, W.J. and Zon, G., Chem. Scripta, 26 (1986) 251.
Guga, P.A., Koziolkiewicz, M., Okruszek, A., Uznanski, B. and Stec, W.J., Nucleos. Nucleot., 6 (1987) 111.
Abramova, T.V., Komarova, N.I., Lebedev, A.V. and Tagay, S.A., Bioorg. Khim., 10 (1984) 1366.
Stawinski, J. and Thelin, M., J. Org. Chem., 59 (1994) 130.
Stec, W.J., Zon, G., Egan, W. and Stec, B., J. Am. Chem. Soc., 106 (1984) 6077.
Potter, B.V.L., Connolly, B.A. and Eckstein, F., Biochemistry, 22 (1983) 1369.
Potter, B.V.L., Romaniuk, P.J. and Eckstein, F., J. Biol. Chem., 258 (1983) 1758.
Bryant, R.F. and Benkovic, S.J., Biochemistry, 18 (1979) 2825.
Burgers, P.M.J. and Eckstein, F., Proc. Natl. Acad. Sci. USA, 75 (1978) 4798.
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.
Ferguson, D.M. and Kollman, P.A., Antisense Res. Dev., 1 (1991) 243.
Durand, M., Maurizot, J.C., Asseline, U., Barbier, C., Thuong, N.T. and Hélène, C., Nucleic Acids Res., 17 (1989) 1823.
Abramova, T.V., Vorobyov, Yu.N. and Lebedev, A.V., Bioorg. Khim., 12 (1986) 1335.
Vorobyov, Yu.N., Molekularnaya Biol., 24 (1990) 58.
Hausheer, F.H., Singh, U.C., Palmer, T.C. and Saxe, J.D., J. Am. Chem. Soc., 112 (1990) 9468.
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.
Hausheer, F.H., Rao, B.G., Saxe, J.D. and Singh, U.C., J. Am. Chem. Soc., 114 (1992) 3201.
Swarnalatha, Y. and Yathindra, N., J. Biomol. Struct. Dyn., 10 (1993) 1023.
Kibler-Herzog, L., Kell, B., Zon, G., Shinozuka, K., Mizan, S. and Wilson, W.D., Nucleic Acids Res., 18 (1990) 3545.
Jaroszewski, J.W., Syi, J.-J., Maizel, J. and Cohen, J.S., Anti-Cancer Drug Des., 7 (1992) 253.
Miller, P.S., Annan, N.D., McParland, K.B. and Pulford, S.M., Biochemistry, 21 (1982) 2507.
Arnold Jr., L., First International Antisense Conference of Japan, Kyoto, December 4–7, 1994, Abstract OP-31.
Noble, S.A., Fisher, E.F. and Caruthers, M.H., Nucleic Acids Res., 12 (1984) 3387.
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.
Charubala, R., Pfleiderer, W., Suhadolnik, R.J. and Sobol, R.W., Nucleos. Nucleot., 10 (1991) 383.
Abramova, T.V., Vlassov, V.V., Lebedev, A.V. and Ryte, A.S., FEBS Lett., 236 (1988) 243.
Abramova, T.V., Lebedev, A.V. and Ryte, A.S., Molekularnaya Biol., 22 (1988) 1285.
Abramova, T.V., Knorre, D.G., Lebedev, A.V., Pichko, N.P. and Fedorova, O.S., Bioorg. Khim., 11 (1985) 1642.
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.
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Lebedev, A.V., Wickstrom, E. The chirality problem in P-substituted oligonucleotides. Perspectives in Drug Discovery and Design 4, 17–40 (1996). https://doi.org/10.1007/BF02172106
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DOI: https://doi.org/10.1007/BF02172106