Extremely high purity oligonucleotides and methods of synthesizi

Details Extremely high purity oligonucleotides and methods of synthesizi Extremely high purity oligonucleotides and methods of synthesizi

1997-05-02

2000-07-11

Houtteman, Scott W.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 2534, C07H 2100

Patent

active

060874910

ABSTRACT:
The present invention comprises an improved method of synthesizing oligonucleotides. The method comprises employing dinucleotides (or "dimer blocks") as the basic synthetic unit building block. The method results in extremely high purity oligonucleotides in which the N-1 content is very low, generally less than 1-2% of the full length, N, oligonucleotide. We have found that synthesis using dinucleotide phosphorothioates results in oligonucleotides having very little phosphodiester content. Furthermore, we have found that the amount of dimer required in each coupling step can be less than about 6 and is preferably about 2 equivalents. Synthesis of oligonucleotides according to the dimer block approach described herein can also be conducted without the capping step that has heretofore been deemed necessary after each coupling.

REFERENCES:
patent: 4469863 (1984-09-01), Ts'o et al.
patent: 5003097 (1991-03-01), Beaucage et al.
patent: 5047524 (1991-09-01), Andrus et al.
patent: 5149798 (1992-09-01), Agrawal et al.
patent: 5252723 (1993-10-01), Bhatt
patent: 5616564 (1997-04-01), Rapaport et al.
Agrawal et al., (1987) Tetrahedron Lett., vol. 28, p. 3539.
Agrawal et al., (1988) Proc. Natl. Acad. Sci., vol 85, p. 7079.
Agrawal et al., (1989) Advanced Drug Delivery Reviews, vol. 6, p. 251.
Agrawal et al., (1990) Proc. Natl. Acad. Sci., vol. 87, p. 1401.
Agrawal et al., (1990) Nucleic Acids Res., vol. 18, p. 5419.
Agrawal et al., (1990) Tetrahedron Lett., vol. 31, No. 52, p. 7541-7544.
Agrawal et al., (1991) Prospects for Antisense Nucleic Acid Therapy of Cancer and Aids, p. 143.
Agrawal, Tibtech, vol. 14, p. 376.
Bannwarth, (1985) Helv. Chim. Acta., vol. 68, p. 1907.
Barker et al., (1996) Proc. Natl. Acad. Sci., vol. 93, p. 514.
Beaucage et al., (1981) Tetrahedron Lett., vol. 22, p. 1859.
Bigelow et al., (1990) J. Chromatography, vol. 533, p. 131.
Connolly et al., (1984) Biochemistry, vol. 23, p. 3443.
Cosstick et al., (1985) Biochemistry, vol. 24, p. 3630.
Crea et al., (1978) Prco. Natl. Aca. Sci., vol. 75, p. 5765.
Eckstein and Gish, (1989) Trends Biochem., vol. 14, p. 97.
Field et al., (1995) J. Exp. Opin. Invest. Drugs., vol. 4, p. 799.
Froehler et al., (1988) Nuc. Acid. Res., vol. 16, No. 11, p. 4831-4839.
Helinski et al., (1991) Tetrahedron Lett., vol. 32, p. 4981-4984.
Iyer et al., (1990) J. Org. Chem., vol. 55, p. 4693-4699.
Jager et al., (1988) Biochemistry, vol. 27, p. 7237.
Kambhampati et al., (1993) Antisnese Res. Dev., vol. 3, p. 405.
Katti et al., (1986) Tetrahedron Lett., vol. 27, p. 5327.
Khorana et al., (1979) Science, vol. 203, p. 614.
Khorana et al., (1972) J. Molec. Biol., vol. 72, p. 209.
Kumar et al., (1984) J. Org. Chem., vol. 49, p. 4905.
Lebadev et al., (1990) Tetrahedron Lett., vol. 31, p. 855.
Leiter et al., (1990) Proc. Natl. Acad. Sci., vol. 87, p. 3430-3434.
Manson et al., Lyphokine Res., vol. 9, p. 35.
Marugg et al., (1984) Nucleic Acid Res., vol. 12, p. 9095.
Metelev et al., (1992) Anal. Biochem., vol. 200, p. 342.
Metelev et al., (1992) Ann. N.Y. Acad. Sci., vol. 660, p. 321-323.
Miura et al., (1987) Chem. Pharm. Bull., vol. 35, p. 833.
Majumdar et al., (1989) Biochemistry, vol. 28, p. 1340.
Nesterova et al., (1995) Nat. Med., vol. 1, p. 528.
Offensperger et al., (1993) EMBO J., p. 1257.
Ohtsuka et al., (1982) Nucleic Acids Res., vol. 10, p. 6553.
Reed et al., (1990) Cancer Res., vol. 50, p. 6565.
Reese, (1978) Tetrhedron Lett., vol. 34, p. 3143.
Roelen et al., (1988) Nucleic Acids Res., vol. 16, p. 7633.
Roelen et al., (1992) Tetrahedron Lett., vol. 33, p. 2357.
Stec et al., (1990) J. Chromatography, vol. 326, p. 263.
Uhlman et al., (1990) Chem. Rev., vol. 90, p. 543.
Wolfgang et al., (1987) Tetrahedron Lett., vol. 28, p. 3205-3208.
Wolter et al., (1986) Nucleosides and Nucleotides, vol. 5, p. 65.
Zamecnik et al., (1978) Proc. Natl. Acad., vol. 75, p. 280.
Zamecnik et al., (1991) Annual Review of AIDS Research, p. 301.
Krotz et al., (1996) Bioorganic & Medicinal Chemistry Letters, vol. 7, No. 1, p. 73-78.
Krotz et al., Bioorg. Med. Chem. Lett. 7(1):73-78, Abstract, Jan. 1997.

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