Acyclic analogs of nucleosides based on tris(hydroxymethyl)phosphine oxide: Synthesis and incorporation into short DNA oligomers

Abstract

Tris-(hydroxymethyl)phosphine oxide (THPO) to a certain extent resembles a part of 2′-deoxyribofuranose, although it exists in an acyclic form only and the oxygen atom at the THPO phosphorus center provides additional hydration site or acceptor of hydrogen bonds. After proper protection of hydroxyl groups, THPO was functionalized with nucleobases and converted into phosphoramidite monomers suitable for incorporation into growing oligonucleotide chains within the solid phase synthesis protocol. The resultant THPO-DNA analogs show reduced affinity to complementary DNA strands, and are resistant towards snake venom and calf spleen exonucleases.