title: Stereocontrolled solid-phase synthesis of phosphorothioate oligoribonucleotides using 2'-O-(2-cyanoethoxymethyl)-nucleoside 3'-O-oxazaphospholidine monomers.
abstract: A method for the synthesis of P-stereodefined phosphorothioate oligoribonucleotides (PS-ORNs) was developed. PS-ORNs of mixed sequence (up to 12mers) were successfully synthesized by this method with sufficient coupling efficiency (94-99%) and diastereoselectivity (≥98:2). The coupling efficiency was greatly improved by the use of 2-cyanoethoxymethyl (CEM) groups in place of the conventional TBS groups for the 2'-O-protection of nucleoside 3'-O-oxazaphospholidine monomers. The resultant diastereopure PS-ORNs allowed us to clearly demonstrate that an ORN containing an all-(Rp)-PS-backbone stabilizes its duplex with the complementary ORN, whereas its all-(Sp)-counterpart has a destabilizing effect.
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Bioscience Building 702, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Nukaga
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamada
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ogata
authors.forename: Natsuhisa
authors.initials: N
authors.lastname: Oka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wada
mesh_terms: D046911:Macromolecular Substances; D009705:Nucleosides / Q000737:chemistry*; D009843:Oligoribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D010080:Oxazoles / Q000737:chemistry*; D010710:Phosphates / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques; D013237:Stereoisomerism; D013873:Thionucleotides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C470122:(1,3,2)oxazaphospholidine; D046911:Macromolecular Substances; D009705:Nucleosides; D009843:Oligoribonucleotides; D010080:Oxazoles; D010710:Phosphates; D013873:Thionucleotides; C035638:thiophosphoric acid