Oligonucleotides having chiral phosphorus linkages
AssigneeIsis Pharmaceuticals, Inc.
InventorPhillip Dan Cook
Life of this patent
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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 SN.sub.2 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.
Claims16
An oligonucleotide comprising a plurality of nucleoside units linked together via phosphate linkages, wherein:
- at least one of the nucleoside units is a non-naturally occurring nucleoside unit;
- and
- at least two of the nucleoside units are linked via chiral phosphate linkages.
An oligonucleotide comprising a plurality of nucleoside units linked together by all S.sub.p phosphotriester linkages or by all R.sub.p phosphotriester linkages.
An oligonucleotide comprising a plurality of linked of nucleoside units linked together by all S.sub.p phosphoramidate linkages or by all R.sub.p phosphoamidate linkages.
An oligonucleotide comprising at least 10 nucleoside units linked together by all S.sub.p alkylphosphonate linkages or by all R.sub.p alkylphosphonate linkages.
Dependencies are inferred from the claim text.