The chirality problem in P-substituted oligonucleotides

P-substituted oligonucleotides, which are oligonucleotide analogs where one (or more) bridging or nonbridging oxygen(s) of an internucleotide bond is substituted by another atom or group of atoms, are being studied as novel potential therapeutics. A chirality problem associated with the substitution of nonbridging oxygen is discussed. Synthesis, structure, hybridization and biological properties of the individual diastereomers of P-substituted oligonucleotides are reviewed.