Hybridization Properties of a DeoxyoIigonucleotide Containing Four Formacetal Linkages

Abstract

Abstract The deoxyoiigonucleotide “TCTCTCTCTCT” bearing four formacetal linkages has been synthesized. The hybridization properties of this compound with complementary RNA and single stranded DNA has been compared to control sequences bearing phosphodiester, phosphoramidate and methylphosphonate linkages. The formacetal oligomer hybridizes to RNA similarly to a diester and significantly better than the other neutral linkages. Recently we reported the synthesis of a deoxyoligonucleotide bearing two formacetal linkages at the three prime end (1). This oligomer was characterized for binding to a complementary RNA sequence. We now report the synthesis of the sequence 5′ TCTC∗TC∗TC∗TCTTT where C is 5 methyl deoxycytidine and ∗ is the formacetal linkage. Controls were prepared in which the modified linkage position ∗ was the normal phosphodiester, methylphosphonate and methoxyethyl phosphoramidate. These four sequences which differ only in the backbone linkage at the starred positions were compared for their ab...