The stability of P-stereodefined PS-(DNA/GNA) duplexes depends on the stereochemistry of the phosphorus centers and arrangement of –^GN_PS– units in the strands.

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.

This review summarizes the synthetic efforts on acyclic analogs of nucleic acids and provides information on the most interesting features of selected classes of such compounds. The selection includes the following types of analogs: Flexible (FNA), Unlocked (UNA), Glycol (GNA), Butyl (BuNA), Threoninol (TNA) and Serinol Nucleic Acids (SNA). These classes of analogs are discussed in terms of their synthetic methods, the thermal stability of their homo- and hetero-duplexes and their applicability in biological and biochemical research and nanotechnology.