| 摘要 |
Sequence-specific oligonucleotides are provided having substantially pu re chiral Sp phosphorothioate, chiral Rp phosphorothioate, chiral Sp alkylphosphociate, 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 o f a phosphodiester, phosphorothioate, phosphoramidate, phosphotriester, or alkyl - phosphate anion on the 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. Alternatively, enzymatic methods are used to prepare oligonucleotides havi ng chirally pure phosphorus inter-sugar linkages. Therapeutic and diagnostic methods using the same are also provided.
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