Synthesis and hybridizing properties of P-stereodefined chimeric [PS]-{DNA:RNA} and [PS]-{DNA:(2'-OMe)-RNA} oligomers.

Oxathiaphospholane derivatives of 2'-OMe-ribonucleosides and 2'- O -TBDMS-ribonucleosides ( M N-OTP and T N-OTP, respectively; nucleobase protected) were synthesized and separated into pure P-diastereomers. X-ray analysis showed the R P absolute configuration of the phosphorus atom in the fast -eluting diastereomer of T A-OTP. The fast - and slow -eluting P-diastereomers of M N-OTP and T N-OTP were used in the solid-phase synthesis of phosphorothioate dinucleotides ( M N PS T and N PS T, respectively), which were subsequently hydrolyzed with R P -selective phosphodiesterase svPDE and S P -selective nuclease P1 to determine the absolute configuration of the phosphorus atoms. P-Stereodefined phosphorothioate ([PS]) 10-mer chimeric oligomers [PS]-{DNA:(2'-OMe)-RNA} and isosequential [PS]-{DNA:RNA} containing two M N PS or N PS units were synthesized. Melting experiments performed for their complexes with Watson-Crick paired DNA matrix showed that M N PS or N PS units decrease the thermal stability of the duplexes (Δ T m = -0.5 ÷ -5.5 °C per modification) regardless of the absolute configuration of the P-atoms. When the (2'-OMe)-RNA matrix was used an increase in T m was noted in all cases (Δ T m = +1 ÷ +7 °C per modification). The changes in thermal stability of the duplexes formed by [PS]-chimeras with DNA and (2'-OMe)-RNA matrices do not correlate with the absolute configuration of the phosphorus atoms.