Oligonucleotides having chiral phosphorus linkages
First Claim
1. An oligonucleotide comprising a plurality of nucleoside units linked together via phosphate linkages, wherein:
- at least two of the nucleoside units are linked via a chiral phosphate linkage;
at least one of said chiral phosphate linkages being between the 3′
-terminal nucleosicle and its adjoining nucleoside; and
with the proviso that said oligonucleotide has less than all of said nucleoside units linked together by either all Rp or all Sp linkages.
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Abstract
Sequence-specific oligonucleotides are provided having substantially pure chiral Sp phosphorothioate, chiral Rp phosphorothioate, chiral Sp alkylphosphonate, chiral Rp alkylphosphonate, chiral Sp phosphoamidate, chiral Rp phosphoamidate, chiral Sp phosphotriester, and chiral Rp phosphotriester linkages. The novel oligonucleotides are prepared via a stereospecific SN2 nucleophilic attack of a phosphodiester, phosphorothioate, phosphoramidate, phosphotriester or alkylphosphonate anion on the 3′ position of a xylonucleotide. The reaction proceeds via inversion at the 3′ position of the xylo reactant species, resulting in the incorporation of phosphodiester, phosphorothioate, phosphoramidate, phosphotriester or alkylphosphonate linked ribofuranosyl sugar moieties into the oligonucleotide.
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Citations
10 Claims
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1. An oligonucleotide comprising a plurality of nucleoside units linked together via phosphate linkages, wherein:
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at least two of the nucleoside units are linked via a chiral phosphate linkage;
at least one of said chiral phosphate linkages being between the 3′
-terminal nucleosicle and its adjoining nucleoside; and
with the proviso that said oligonucleotide has less than all of said nucleoside units linked together by either all Rp or all Sp linkages. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
at least one of the nucleoside units is selected from the group consisting of wherein; Q is O or CHRG;
RA and RB are H, lower alkyl, substituted lower alkyl;
RC is H, OH, lower alkyl, substituted lower alkyl, F, Cl, Br, CN, CF3, OCF3, SOMe, SO2Me, ONO2, NO2, N3, NH2, NH-alkyl, substituted NH-alkyl, OCH2CH═
CH2, OCH═
CH2, OCH2CCH, OCCH, aralkyl, heteroaralkyl, heterocycloaryl, polyalkylamino and substituted silyl;
RG is H, lower alkyl and substituted lower alkyl; and
BX is a naturally occurring or synthetic nucleoside base.
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Specification