Nissan Chemical Corporation

Nissan Chemical Industries Limited

Tokyo Institute of Technology

Tokyo University of Pharmacy & Life Sciences

Yusuke Iriyama

Tatsuro Kanaki

Hiroyuki Nakajima

Yoshikazu Ootsuka

Akiko Yamazaki

Keita Yoshida

Kohji Seio

Tsutomu Higashiyama

Keishi Yamamoto

Shunsuke Shiraishi

Ei Nakata

Keiichiro Otsuka

Hisako Ibaraki

Yuuki Takashima

Tomohiro Akeboshi

Takanori Kanazawa

Masatoshi Niwa

Yoshiaki Masaki

The invention provides a single-stranded oligonucleotide represented by the formula (I), wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified-nucleotide, and has a first nucleotide sequence capable of hybridizing with a second oligonucleotide. Y is composed of 4 to 100 nucleotides, enables hybridization with the above-mentioned first oligonucleotide, and has a second nucleotide sequence containing at least one ribonucleotide. At least one of the nucleotide sequences X, Xz and Y has an antisense sequence capable of hybridizing with a target RNA. At least one of L, Lx and Ly is a linking group that contains a non-nucleotide structure. 

Single-stranded oligonucleotide

The invention provides a single-stranded oligonucleotide represented by the formula [Xz-Lx]-X-Y-[Ly-Yz], wherein X is represented by Xa-Xb, Xa is coupled with Y, and Xb and Y hybridize. Xa is composed of 1 to 40 nucleotides and contains at least one modified-nucleotide. Xb is composed of 4 to 40 nucleotides and contains at least one modified-nucleotide. Y is composed of 4 to 40 nucleotides and contains at least one ribonucleotide. Xz and Yz are composed of 5 to 40 nucleotides and contain at least one modified-nucleotide. Nucleotide sequences X, Xz and Yz have an antisense sequence capable of hybridizing with a target RNA. Lx and Ly are composed of 0 to 20 nucleotides.

Provided is a single-stranded oligonucleotide that is capable of controlling a target gene with high efficiency and can be easily produced. The single-stranded oligonucleotide is represented by the formula X-L-Y wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified nucleotide, and has a first nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least four contiguous nucleotides recognized by RNase H. Y is composed of 4 to 100 nucleotides, and has a second nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least one ribonucleotide. At least one of nucleotide sequence X and nucleotide sequence Y has an antisense sequence capable of hybridizing with a target RNA. L is a group derived from a third oligonucleotide that is degraded under physiological conditions.

Provided is an artificial nucleoside or artificial nucleotide capable of composing an artificial oligonucleotide having superior nuclease resistance. The artificial nucleoside or artificial nucleotide is a compound represented by formula (I) or a salt thereof (wherein, Bx represents a pyrimidine base or purine base, R, R, Rand Rrepresent hydrogen atoms, C1-6 alkyl groups or the like, Y represents NRR(wherein, Rand R, independently of each other, represent a hydrogen atom, C1-6 alkyl group or the like, or Rand R, together with a nitrogen atom bound thereto, form a 3- to 11-membered nitrogen-containing non-aromatic heterocyclic group) or an optionally substituted C2-9 aromatic heterocyclic group, Zand Zrepresent hydrogen atoms, hydroxyl group-protecting groups, phosphorous-containing groups or the like, and n represents an integer of 1 to 3).

Artificial nucleoside and artificial nucleotide, and artificial oligonucleotide

This is to provide a composition for delivering a nucleic acid and a nucleic acid-containing composition which ensure stability of a nucleic acid drug, have a high intracellular introduction rate, can efficiently express the function of a nucleic acid drug, and have low cytotoxicity. Disclosed is a composition for delivering a nucleic acid and a nucleic acid-containing composition each comprises a block copolymer in which a polyethylene glycol segment and a hydrophobic polyester segment are linked, and a peptide having 4 to 30 residues containing at least one selected from the group consisting of arginine and lysine.

Composition for delivering nucleic acid and nucleic acid-containing composition

The invention provides a process for producing a &#x3b2;-dihydrofuran derivative represented by formula (1) or a &#x3b2;-tetrahydrofuran derivative represented by formula (4), characterized in that the process includes causing a dialkyl dicarbonate, a diaralkyl dicarbonate, or a halide to act on a diol compound represented by formula (2) or (3). The invention also provides a process for producing 4'-ethynyl-2&#x2032;,3&#x2032;-didehydro-3&#x2032;-deoxythymidine or an analog thereof, the process including glycosylation and deprotection. 

Certain &#x3b2;-dihydrofuran derivatives

The invention provides a process for producing a &#x3b2;-glycoside compound represented by formula (3), characterized in that the process includes causing to react a cyclic alkene compound represented by formula (1) or (2) with a nucleophile in the presence of a transition metal catalyst. 

Process for preparation of &#x3b2;-glycoside compounds

An acylating agent and a hydrolase are caused to act on a hydroxypyranone represented by formula (I) in a water-containing organic solvent, to thereby produce an acyloxypyranone compound represented by formula (II) (wherein Rrepresents an acyl group). Then, an acetylene organic metal compound represented by formula (III) (wherein Rrepresents a hydrogen atom or a tri-substituted silyl group, and M represents an alkali metal atom, aluminum, or a magnesium monohalide) and a coordinating additive are caused to act on the acyloxypyranone compound represented by formula (II), to thereby produce an alkyne compound represented by formula (IV). The alkyne compound represented by formula (IV) is hydrolyzed with acid, to thereby produce a dihydrofuran compound represented by formula (V). 

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Funabashi, Japan

Yusuke Iriyama