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 (^MN-OTP and ^TN-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 ^TA-OTP. The fast- and slow-eluting P-diastereomers of ^MN-OTP and ^TN-OTP were used in the solid-phase synthesis of phosphorothioate dinucleotides (^MN_PST and N_PST, 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 ^MN_PS or N_PS units were synthesized. Melting experiments performed for their complexes with Watson-Crick paired DNA matrix showed that ^MN_PS or N_PS units decrease the thermal stability of the duplexes (ΔT _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 (ΔT _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.