DIISOPROPYLSILYL-LINKED OLIGONUCLEOTIDE ANALOGS - SOLID-PHASE SYNTHESIS AND PHYSICOCHEMICAL PROPERTIES

A novel synthetic method has been developed for efficient preparation of silyl-linked oligodeoxyribonucleotide analogs. The method allows, f or the first time, automated solid-phase synthesis of long oligomers u niformly linked with the silyl internucleoside bridge. Synthesis of a thymidylate decanucleotide analog (14) illustrates this advance. The p reparation of chimeric oligodeoxyribonucleotides containing single or multiple diisopropylsilyl backbone structures along with natural phosp hodiester links is also described. These mixed backbone DNA strands we re soluble and chemically stable in buffered aqueous solutions, as req uired for physicochemical study. These oligomers demonstrated excellen t stability toward cleavage by 3'-exonuclease and good binding affinit y with complementary oligonucleotides.