Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nu

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

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536 231, 536 241, 536 243, 435 6, 435911, C07H 2104, C12Q 168, C12P 1934

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055960910

ABSTRACT:
Replacement of the natural nucleotides with unnatural zwitterionic nucleotides having a cationic moiety tethered to the base (or analog thereof) results in oligodeoxynucleotides with diminished charge but undiminished ability to complex with DNA at low ionic strengths. We have now discovered that DNA can be made fully zwitterionic by introducing tethered cationic moieties to the bases without affecting duplex formation. The resulting oligonucleotides have the further advantages of being nuclease resistant.

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Uhlman, Eugen, et al. (1990) "Antisense Oligonucleotides: A New Therapeutic Principle," Chemical Reviews, 90:543-584.
Hashimoto, Hiromasa, et al. (1993), "Formation of Chimeric Duplexes between Zwitterionic and Natural DNA," J. Org. Chem., 58:4194-4195.
Hashimoto, Hiromasa, et al. (1993), "Zitterionic DNA," J. Am. Chem. Soc. 115:7128-7134.

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