Oligonucleotide analogues with a nucleobase-including backbone part 5 - 2 '-deoxy-8-(hydroxymethyl)adenosine- and 2 '-deoxy-6-(hydroxymethyl)uridine-derived phosphoramidites: Synthesis and incorporation into 14-mer DNA strands

The pairing propensity of new DNA analogues with a phosphinato group betwee n O-C(3') and a newly introduced OCH, group at C(8) and C(6) of 2'-deoxyade nosine and 2'-deoxyuridine. respectively, was evaluated hy force-field calc ulations and Maruzen model studies. These studies suggest that these analog ues may form autonomous pairing systems, and that the incorporation of sing le: modified units into DNA 14mers is compatible with duplex formation. To evaluate the incorporation. we prepared the required phosphoramidites 3 and 4 from 2'-deoxyadenosine and 2'-deoxyuridine, respectively. The phosphoram idite 5 was similarly prepared to estimate the influence of a CH,OH group a t C(8) on the duplex stability. The modified 14-mers 6-9 were prepared by s olid-phase synthesis. Pairing studies show a decrease of the melting temper ature by 2.5 degrees for the duplex 13.9, and of 6-8 for the duplexes 10.6, 11.6, 13.7 and 14.8, as compared to the unmodified duplexes.