Stereocontrolled solid-phase synthesis of phosphorothioate oligoribonucleotides using 2'-O-(2-cyanoethoxymethyl)-nucleoside 3'-O-oxazaphospholidine monomers. 2012

Yohei Nukaga, and Kohei Yamada, and Toshihiko Ogata, and Natsuhisa Oka, and Takeshi Wada
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.

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.

UI MeSH Term Description Entries
D009705 Nucleosides Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleoside,Nucleoside Analog,Nucleoside Analogs,Analog, Nucleoside,Analogs, Nucleoside
D009843 Oligoribonucleotides A group of ribonucleotides (up to 12) in which the phosphate residues of each ribonucleotide act as bridges in forming diester linkages between the ribose moieties.
D010080 Oxazoles Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions. Oxazole,1,3-Oxazolium-5-Oxides,Munchnones,1,3 Oxazolium 5 Oxides
D010710 Phosphates Inorganic salts of phosphoric acid. Inorganic Phosphate,Phosphates, Inorganic,Inorganic Phosphates,Orthophosphate,Phosphate,Phosphate, Inorganic
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D013873 Thionucleotides Nucleotides in which the base moiety is substituted with one or more sulfur atoms.
D046911 Macromolecular Substances Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure. Macromolecular Complexes,Macromolecular Compounds,Macromolecular Compounds and Complexes,Complexes, Macromolecular,Compounds, Macromolecular,Substances, Macromolecular
D060327 Solid-Phase Synthesis Techniques Techniques used to synthesize chemicals using molecular substrates that are bound to a solid surface. Typically a series of reactions are conducted on the bound substrate that results in either the covalent attachment of specific moieties or the modification of existing function groups. These techniques offer an advantage to those involving solution reactions in that the substrate compound does not have to be isolated and purified between the reaction steps. Solid-Phase Synthesis,Peptide Synthesis, Solid-Phase,Solid-Phase Nucleotide Synthesis,Solid-Phase Nucleotide Synthesis Techniques,Solid-Phase Peptide Synthesis,Solid-Phase Peptide Synthesis Techniques,Solid-Phase Synthesis Methods,Synthesis, Solid-Phase,Method, Solid-Phase Synthesis,Methods, Solid-Phase Synthesis,Nucleotide Syntheses, Solid-Phase,Nucleotide Synthesis, Solid-Phase,Peptide Syntheses, Solid-Phase,Peptide Synthesis, Solid Phase,Solid Phase Nucleotide Synthesis,Solid Phase Nucleotide Synthesis Techniques,Solid Phase Peptide Synthesis,Solid Phase Peptide Synthesis Techniques,Solid Phase Synthesis,Solid Phase Synthesis Methods,Solid Phase Synthesis Techniques,Solid-Phase Nucleotide Syntheses,Solid-Phase Peptide Syntheses,Solid-Phase Syntheses,Solid-Phase Synthesis Method,Solid-Phase Synthesis Technique,Syntheses, Solid-Phase,Syntheses, Solid-Phase Nucleotide,Syntheses, Solid-Phase Peptide,Synthesis Method, Solid-Phase,Synthesis Methods, Solid-Phase,Synthesis Technique, Solid-Phase,Synthesis Techniques, Solid-Phase,Synthesis, Solid Phase,Synthesis, Solid-Phase Nucleotide,Synthesis, Solid-Phase Peptide,Technique, Solid-Phase Synthesis,Techniques, Solid-Phase Synthesis

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