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'--TBDMS-ribonucleosides (N-OTP and N-OTP, respectively; nucleobase protected) were synthesized and separated into pure P-diastereomers. X-ray analysis showed the absolute configuration of the phosphorus atom in the -eluting diastereomer of A-OTP. The - and -eluting P-diastereomers of N-OTP and N-OTP were used in the solid-phase synthesis of phosphorothioate dinucleotides (NT and NT, respectively), which were subsequently hydrolyzed with -selective phosphodiesterase svPDE and -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 N or N units were synthesized. Melting experiments performed for their complexes with Watson-Crick paired DNA matrix showed that N or N units decrease the thermal stability of the duplexes (Δ = -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 was noted in all cases (Δ = +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.