Novel linear and branched oligodeoxynucleotide analogues containing 4′-c-(hydroxymethyl)thymidine

Article abstract of DOI:10.1016/0040-4020(95)00606-9

4′-C-(Hydroxymethyl)thymidine has been incorporated into novel linear and branched oligodeoxynueleotide (ODN) analogues by use of the phosphoramidite synthons 4, 7 and 11. ODNs containing modification X (from amidite 4, unnatural 5′-hydroxy to 4′-C-hydroxymethyl backbone) displayed significantly decreased thermal stabilities towards complementary DNA compared to unmodified controls. On the contrary, ODNs containing modification Y (from amidite 7, natural 5′-hydroxyl to 3′-hydroxyl backbone) formed highly stable duplexes towards both complementary DNA and RNA. Phosphoramidite 11 containing two dimethoxytrityl protective groups was used for fully automated synthesis of a branched ODN analogue containing identical sequences in two out of the three branches originating from the branching point (modification Z). Branched ODN S exhibited only moderately decreased thermal stability (towards complementary linear DNA) compared to the linear reference (ODN R). This demonstrates the versatility of the additional 4′-C-hydroxymethyl functionality (in modification Y) as an attachment point for introduction of molecular entities pointing into the minor groove of a DNA:DNA duplex.