Synthesis and duplex stability of oligodeoxynucleotides containing stereoregular or stereorandom octylphosphonate linkages

Article abstract of DOI:10.1016/0040-4020(96)00532-7

The synthesis of oligodeoxynucleotide pentadecamers containing two octylphosphonate linkages [3'-O-P(=O)(n-C₈H₁₇)-O-5'] with stereoregular or stereorandom chirality is described. The introduction of random octylphosphonate linkages was performed using a monomeric nucleoside octylphosphonamidite as synthon whereas the introduction of stereoregular linkages could be accomplished by the use of stereoregular dimers containing a preformed octylphosphonate linkage. The novel oligodeoxynucleotides were characterized by electrospray ionization mass spectrometry and the influence of chirality of the modified linkages on the duplex stability was studied. Furthermore, end-capped oligodeoxynucleotides having two octylphosphonate linkages at either end which were directed against HSV-1 mRNA have been synthesized for investigation as antisense drugs.