Oligonucleotide N3.fwdarw.P5' phosphoramidates: triplex DNA form

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing compound containing saccharide radical

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536 231, 536 241, 536 245, 435 6, C12P 1934, C12Q 168, C07H 2104

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055916074

ABSTRACT:
Modified oligonucleotides 3'-NHP(O)(O.sup.-)O-5' phosphoramidates were synthesized on a solid phase support. The phosphoramidate analogs were found to have significantly increased resistance toward phosphodiesterase digestion. Thermal dissociation experiments demonstrated that these compounds form more stable duplexes than phosphodiesters with complementary DNA and particularly RNA strands. Further, the phosphoramidate analogs can also form stable triplexes with double-stranded DNA target, where under similar conditions parent phosphodiester compounds failed to do so.

REFERENCES:
patent: 5176996 (1993-01-01), Hogan et al.
patent: 5256775 (1993-10-01), Froehler
patent: 5264564 (1993-11-01), Matteucci
patent: 5271941 (1993-12-01), Cho-Chung
patent: 5476925 (1995-12-01), Letsinger et al.
Gura et al. (1995) Science 270:575-577. "Antisense has growing pains".
Gryaznov et al. (1992) "Synthesis and properties of oligonucleotides containing amino deoxythymidine units" Nucleic Acids Res. 20:3403-3409.
Cooney et al. (1988) "Site-specific oligonucleotide binding represses transcription of the human c-myc gene in vitro" Science 241:456-459.
Uhlmann et al. (1990) "Antisense oligonucleotides: A new therapeutic principle" Chem. Rev. 90:544-584.
Milligan et al. (1993) "Current Concepts in Antisense Drug Design" J Med. Chem. 36:1923-1937.
Ratajczak, et al, "In Vivo Treatment of Human Leukemia in a Scid Mouse Model with C-myb Antisense Oligodeoxynucleotides," (1992), Proc. Natl. Acad. Sci. USA, vol. 89, pp. 11823-11827.
Szczylik, et al, "Selective Inhibition of Leukemia Cell Proliferation by BCR-ABL Antisense Oligonucleotides," (1991), Science, vol. 253, pp. 562-565.
Zielinski, et al, "Autocatalytic Synthesis of a Tetranucleotide Analog," (1987), Nature (London), vol. 327, No. 6120, pp. 346-347.
Mag, et al, "Synthesis and Selective Cleavage of an Oligonucleotide Containing a Bridged Non-Chiral Internucleotide 3'-Phosphoramidate Linkage," (1992), Tetrahedron Letters, vol. 33, No. 8, pp. 7319-7322.
Agrawal et al, "Oligodeoxynucleoside Phosphoramidates and Phosphorothioates as Inhibitors of Human Immunodeficiency Virus," (1988), Proc. Natl. Acad. Sci., vol. 85, pp. 7079-7083.
Dagle, et al, "Physical Properties of Oligonucleotides Containing Phosphoramide-Modified Internucleoside Linkage," (1991), Nuclaic Acids Research, vol. 1, N. 8, pp. 1805-1810.
Mag, et al, "Synthesis of Dinucleotides Containing a bridged Non-Chiral Internucleotides 5'- or 3'-Phosphoramidate Linkage," (1994) Tetrahedron Letters, vol. 50, No. 34, pp. 10225-10234.
Zielinski, et al, "Oligoaminonucleoside Phosphoramidates, Oligomerization of Dimers of 3'- Amino-3'Deoxy-Nucleotides (GC and CG) in Aqueous Solution," (1987), Nucleic Acids Research, vol. 15, No. 4, pp. 1699-1715.

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