Synthesis and properties of α- and β-oligodeoxynucleotides containing α- and β-1-(2-O-methyl-d-arabinofuranosyl)thymine Original Research Article

Synthesis of the α- and β-anomer of 2′-OMe-araT (α- and β-1-(2-O-methyl-d-arabinofuranosyl)thymine) and their incorporation into oligodeoxynucleotide (ODN) analogues is described. Condensation of the key arabinofuranose derivative with silylated thymine afforded the α-anomer and the β-anomer which were converted into the respective phosphoramidite building blocks. Automated synthesis of β-ODNs containing β-2′-OMe-araT (by use of standard β-amidites and phosphoramidite building block 9b) and α-ODNs containing α-2′-OMe-araT (by use of α-T-amidite and phosphoramidite building block 9a) allowed evaluation of their properties. With regard to 3′-exonucleolytic degradation, 3′-end incorporation of either β- or α-2′-OMe-araT resulted in considerable stabilization compared to unmodified β-ODNs. Thermal stabilities of duplexes formed between modified ODNs and both unmodified DNA and RNA were evaluated and compared to unmodified controls. In all experiments stable duplexes were formed, but whereas β-ODNs containing β-2′-OMe-araT showed moderately lowered thermal stabilities towards both DNA and RNA, α-ODNs containing α-2′-OMe-araT exhibited significantly increased melting points (compared to β-ODN controls) when complexed with RNA. These results illustrate the potential of using arabino-configurated nucleosides as modified monomers in biologically active ODN-analogues, either as, e.g., 2′-O-alkylated or 2′-O-functionalized derivatives.