SYNTHESIS AND DUPLEX STABILITY OF OLIGODEOXYNUCLEOTIDES CONTAINING STEREOREGULAR OR STEREORANDOM OCTYLPHOSPHONATE LINKAGES

The synthesis of oligodeoxynucleotide pentadecamers containing two oct ylphosphonate linkages [3'-O-P(=O)(n-C8H17)-O-5'] with stereoregular o r stereorandom chirality is described The introduction of random octyl phosphonate linkages was performed using a monomeric nucleoside octylp hosphonamidite as synthon whereas the introduction of stereoregular li nkages could be accomplished by the use of stereoregular dimers contai ning a preformed octylphosphonate linkage. The novel oligodeoxynucleot ides were characterized by electrospray ionization mass spectrometry a nd the influence of chirality of the modified linkages on the duplex s tability was studied. Furthermore, end-capped oligodeoxynucleotides ha ving two octylphosphonate linkages at either end which were directed a gainst HSV-1 mRNA have been synthesized for investigation as antisense drugs. Copyright (C) 1996 Elsevier Science Ltd