title: Synthesis and properties of alpha- and beta-oligodeoxynucleotides containing alpha- and beta-1-(2-O-methyl-D-arabino-furanosyl)thymine.
abstract: Synthesis of the alpha- and beta-anomer of 2'-OMe-araT (alpha- and beta-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 alpha-anomer and the beta-anomer which were converted into the respective phosphoramidite building blocks. Automated synthesis of beta-ODNs containing beta-2'-OMe-araT (by use of standard beta-amidites and phosphoramidite building block 9b) and alpha-ODNs containing alpha-2'-OMe-araT (by use of alpha-T-amidite and phosphoramidite building block 9a) allowed evaluation of their properties. With regard to 3'-exonucleolytic degradation, 3'-end incorporation of either beta- or alpha-2'-OMe-araT resulted in considerable stabilization compared to unmodified beta-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 beta-ODNs containing beta-2'-OMe-araT showed moderately lowered thermal stabilities towards both DNA and RNA, alpha-ODNs containing alpha-2'-OMe-araT exhibited significantly increased melting points (compared to beta-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.
authors.affiliation: Department of Chemistry, Odense University, Denmark.
authors.forename: C H
authors.initials: CH
authors.lastname: Gotfredsen
authors.forename: J P
authors.initials: JP
authors.lastname: Jacobsen
authors.forename: J
authors.initials: J
authors.lastname: Wengel
mesh_terms: D001087:Arabinonucleosides / Q000737:chemistry*; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D009841:Oligonucleotides / Q000138:chemical synthesis*; D013936:Thymidine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D001087:Arabinonucleosides; D009841:Oligonucleotides; C010032:thymine arabinoside; D013936:Thymidine