Exonuclease-resistant oligonucleotides

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

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536 231, 536 2533, C07H 2102

Patent

active

052567753

ABSTRACT:
A method is provided for making 3' and/or 5' end-capped oligonucleotides so as to render the oligonucleotide resistant to degradation by exonucleases. The exonuclease degradation resistance is provided by incorporating two or more phosphoramidate and phosphorocmonothioate and/or phosphorodithioate linkages at the 5' and/or 3' ends of the oligonucleotide, wherein the number of phosphoramidate linkages is less than a number which would interfere with hybridization to a complementary oligonucleotide strand and/or which would interfere with RNAseH activity when the oligonucleotide is hybridized to RNA.

REFERENCES:
P. Verspieren et al., Gene 61:307-315 (1987).
Agrawal, Tet. Lett. 28(31):3539-3542 (1987).
Brill et al., Tet. Lett. 29(43):5517-5520 (1988).
Froehler, Tet. Lett. 27(46):5575-5578 (1986).
Froehler et al., Nuc. Acids Res. 14(13):5399-5407 (1986).
Froehler et al., Nuc. Acids Res. 16(11):4831-4839 (1988).
Letsinger et al., Nuc. Acids. Res. 14(8):3487-3499 (1986).

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