Oligonucleotide Analogues with a Nucleobase-Including Backbone 2'-Deoxy-8-(hydroxyethyl)adenosine- and 2'-Deoxy-6-(hydroxymethyl)uridine-Derived Phosphoramidites:Synthesis and Incorporation into 14-Mer DNA Strands

摘要

The pairing propensity of new DNA analogues with a phosphinato group between O-C(3') adn a newly introduced OCH_2 group at C(8) and C(6) of 2'deoxyadenosine adn 2'-deoxyuridine,respectively,was evaluated by force-field calculations and Maruzen model studies.These studies suggest that these analogues may form autonomous piring system,sand that the incorporation of single modified units into DNA 14mers is compatible with duplex formaiton.To evaluate the incorporation,we prepared the required phosphoramidites 3 and 4 from 2'-deoxyadenosine and 2'-deoxyuridine,respectively.The phosphoramidite 5 was similarly prepared to estimate teh influence of a CH_2 OH group at C(8) on the duplex stability.The modified 14-mers 6-9 were prepared by solid-phase synthesis.Pairing sutdies show a decrease of the melting temperature by 2.5deg for the duplex 13centre dot9,and of 6-8deg for the duplexes 10centre dot6,11centre dot6,13centre dot7,and 14centre dot8,as compared to the unmodified duplexes.