Japan Science and Technology Agency

Tokyo Institute of Technology

Mitsuo Sekine

Kohji Seio

Akihiro Ohkubo

Hisao Saneyoshi

Masahiro Mizuta

Takeshi Terada

Takeshi Yamada

Kazushi Sakamoto

Takeshi Sasami

Provided is a ribonucleoside derivative represented by General Formula (I): (wherein Rrepresents a hydrogen atom or the like, Rrepresents a hydrogen atom or the like, Rrepresents a methyl group or the like, and B represents a nucleic acid base residue optionally having a protecting group or a modifying group). An RNA containing this ribonucleoside derivative shows excellent hybridization ability and resistance to nuclease.

2'-hydroxyl group-modified ribonucleoside derivatives

Methods of synthesizing nucleic acid oligomers on a solid-phase support having a 3'-end nucleoside unit introduced thereon-as represented by formula II: wherein of formula II represents a 2&#x2032;-deoxyribonucleoside or its N-protected derivative, the substituent &#x2014;O&#x2014;(R)Si(R)&#x2014;(CHR)&#x2014;(CH)&#x2014;O&#x2014;P(OR)XO)&#x2014;(CH)is attached at the 3&#x2032; position of the sugar moiety of the nucleoside substituent; each of Rand Ris an alkyl or optionally substituted aryl group, wherein the optionally substituted aryl group has a substituent selected from the group consisting of Calkyl, nitro, cyano, halo and methoxyl; Ris a protecting group; X is S or O; Ris H or 4,4&#x2032;-dimethoxytrityl; each n is an integer of from 1 to 5; and the solid-phase support has hydroxyl groups on its surface.

3'-end nucleoside unit comprising phosphoramidite

The purpose of the present invention is to provide a compound that specifically binds to the base sequence of a double-stranded nucleic acid molecule. The compound can reduce the electrochemical signal/noise ratio (S/N) in electrochemical detection, and as a result, the detection sensitivity (precision) will be greatly improved so as to enable the determination of an ultratrace amount of nucleic acid molecule. The present invention relates to a ferrocene compound represented by the following general formula (I): wherein 'A' represents a divalent ferrocene-containing linker or ferrocene-1,1'-yl, Rrepresents a hydrogen atom or alkyl; 'n' and &#x201c;m&#x201d; represent any natural numbers; and &#x201c;V&#x201d; and &#x201c;X&#x201d; represent the pyrrole-imidazole-polyamide (PIPA); to a ligand consisting of said ferrocene compound for sequence-specific detection of double-stranded nucleic acid molecules; to a method for electrochemical detection of double-stranded nucleic acid molecules 8 with the use of said ligand; and to an apparatus or device for the electrochemical detection with the use of said ligand.

Electrochemically active ligand for sequence-specific detection of double-stranded nucleic acid molecule

To provide an oligonucleotide derivative that can be used without a problem of falling of a DNA probe from a support. The oligonucleotide derivative of the present invention is represented by the following General Formula (1). The oligonucleotide derivative of the present invention can be used in a DNA chip, a microarray, and so on and further used in a method of detecting gene and a method of regulating gene expression, for example. 

Oligonucleotide derivative, probe for detection of gene, and DNA chip

A phosphoramidite method for the synthesis of a nucleic acid oligomer without protecting the base moiety characterized in that a 3' or 5&#x2032; hydroxyl group of a nucleotide is reacted with a nucleoside phosphoramidite, a cyclonucleoside phosphoramidite, a 2&#x2032;-substituted nucleoside phosphoramidite, a 4&#x2032;-substituted nucleoside phosphoramidite, or a 2&#x2032;,4&#x2032;-di-substituted nucleoside phosphoramidite to produce a phosphodiester linkage. The phosphoramidite is contacted with an activator containing both a) hydroxybenzotriazole-1-ol (HOBt), a mono-substituted HOBt, a di-substituted HOBt, or a di-substituted phenol and b) imidazole, tetrazole, benzimidazoletriflate (BIT), 4-ethylthiotetrazole, imidazolium triflate(trifluoromethane sulfonate) or 4,5-dicyanoimidazole.

Method for the synthesis of nucleic acid without protecting base moiety

The purpose of the invention is to develop a silyl linker that can be efficiently introduced on a solid-phase support used for the synthesis of nucleic acid oligomers such as DNA. The present invention relates to a silyl linker for use in the solid-phase synthesis of nucleic acid, comprised of a compound of the general formula or its ester or salt:H&#x2014;(R1)Si(R2)-(CH)&#x2014;CONH-(A)-COOH&#x2003;&#x2003;(I)wherein each of R1 and R2 is an alkyl or aryl group, and (A) represents a spacer moiety; a 3'-end nucleoside unit having said compound linked via an oxygen atom to the 3-position of a sugar of the nucleoside or its derivative, a solid-phase support having the 3&#x2032;-end nucleoside unit, and a method for synthesis of nucleic acid oligomer with the use of said solid-phase support.

Silyl linker for solid-phase synthesis of nucleic acid

The purpose of the present invention is to develop a system for efficiently constituting cyanoethyl ethers under mild conditions and probability of the ethers as functional groups for imparting specific functions and to make a contribution to the production of novel functional nucleic acids. The present invention relates to a nucleoside that is represented by the general formula (I) or a nucleotide derived therefrom: wherein X and Y may be the same as or different from each other, and are hydrogen, optionally substituted silyl group, 4-methoxytrityl group, 4,4'-dimethoxytrityl group or a group represented by the general formula (II): wherein R1 and R2 may be the same as or different from each other, representing an alkyl group having 1-7 carbon atoms such as diisopropyl, or they are united with each other to form a ring structure, R3 represents a protective group for a phosphoric acid such as 2-cyanoethyl; and B1 represents an optionally substituted pyrimidine or purine base.

Growing community of inventors

Yokohama, Japan

Mitsuo Sekine