A novel class of oligonucleotide analogues containing 2′-O,3′-C-linked [3.2.0]bicycloarabinonucleoside monomers:: Synthesis, thermal affinity studies, and molecular modeling

Oligonucleotide analogues containing a novel 2'-O,3'-C-linked [3.2.0]bicyclonucleoside have been efficiently synthesized. Enhanced thermal stabilities of duplexes toward both RNA and DNA are reported for a 14-mer oligothymidylate containing 13 modifications and for a nonamer mixed sequence containing three modifications. These results and the results from molecular modeling reveal that strong conformational restriction of a monomer can be important for favorable duplex formation though the fixed conformation of the pentofuranose ring deviates from a North or South conformation.