Oligonucleoside Phosphorothioates

There are three constitutionally isomeric forms of internucleoside phosphorothioate linkages. Replacement of either the 3′- or 5′-oxygen in a phosphodiester linkage, 1 , results in the respective thiolo structures 2 or 3 , whereas substitution of a nonbridging oxygen with sulfur gives a thiono structure 4 . Oligonucleoside thiolo phosphorothioates 2 and 3 , which have an achiral phosphorus moiety and are electronically similar to 1 , are currently not synthesized by automated methods (1 ,2 ) as easily as their thiono counterpart (3 ), 4 . Thiono form 4 also differs from 2 and 3 by having a chiral phosphorus (R _p , S _p ) center and a negative charge localized on sulfur 5 (4 ,5 ).