Oligonucleotide N3'-P5' phosphoramidates: hybridization and nucl

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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536 231, 435 6, C07H 2104, C12Q 168

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active

055999220

ABSTRACT:
Modified oligonucleotide 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: 5271941 (1993-12-01), Cho-Chung
patent: 5476925 (1995-12-01), Letsinger et al.
Mag et al. (1992) "Synthesis and Selective Cleavage of an Oligodeoxynucleotide Containing a Bridged Non-Chiral Internucleotide 3'-Phosphoramidate . . . " Tetrahedron Letters 33: 7319-7322.
Milligan et al. (1993) "Current Concepts in Antisense Drug Design" J. Med. Chem. 36: 1923-1937.
Uhlmann et al (1990) "Antisense Oligonucleotides: A New Therapeutic Principle" Chemical Rev. 90: 543-584.
Dagle et al. (1991)"Physical Properties of Oligonucleotides Containing Phosphoramidates-Modified Internucleotide Linhages". Nucleic Acids Res. 19: 1805-1810.
Gryaznov, et al. Synthesis and Properties of Oligonucleotides Containing Aminodeoxythymidine Units, (1992), Department of Chemistry, Northwestern University, (Nucleic Acids Research) vol. 20, No. 13, pp. 3403-3409.
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), 327 (6120), 346-7 (Abstract).

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