Phosphorothioate Oligonucleotide-Directed Triple Helix Formation

Phosphorothioate oligodeoxyribonucleotides were tested for their ability to recognize double-helical DNA in two distinct triple helix motifs. Purine-rich oligonucleotides containing a diastereomeric mixture of phosphorothioate or stereoregular (all RP) phosphorothioate linkages are shown to form triple-helical complexes with affinities similar to those of the corresponding natural phosphodiester oligonucleotides. In contrast, pyrimidine-rich phosphorothioate oligonucleotides containing a mixture of diastereomeric or stereoregular (all RP) linkages do not bind to double-helical DNA with measurable affinity. These observations have implications for triple helix structure and for biological applications.