The synthesis and binding properties of oligonucleotide analogs containing diastereomerically pure conformationally restricted acetal linkages

The synthesis of 5,6-bicyclic thymine:thymine nucleoside containing a conformationally restricted dioxane acetal has been achieved from 2′-O-allyl 5-methyl uridine. The two diastereomers were separated and incorporated in a single position within an oligonucleotide (ON) sequence. The binding properties of these ONs when hybridized to complementary RNA and DNA were evaluated by thermal denaturation (Tm) analysis. Lower Tms for both diastereomers were obtained when compared to the corresponding control phosphodiester ON.