WO2005087784A1 - 電気化学的に活性な配列特異的二本鎖核酸分子検出用リガンド - Google Patents
電気化学的に活性な配列特異的二本鎖核酸分子検出用リガンド Download PDFInfo
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- WO2005087784A1 WO2005087784A1 PCT/JP2005/003440 JP2005003440W WO2005087784A1 WO 2005087784 A1 WO2005087784 A1 WO 2005087784A1 JP 2005003440 W JP2005003440 W JP 2005003440W WO 2005087784 A1 WO2005087784 A1 WO 2005087784A1
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- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 241000711549 Hepacivirus C Species 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- 229930192627 Naphthoquinone Natural products 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- NPUXORBZRBIOMQ-RUZDIDTESA-N [(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]-2-pyrrolidinyl]methanol Chemical compound C=1C(OCC=2C=CC(CN3[C@H](CCC3)CO)=CC=2)=CC(C)=CC=1CS(=O)(=O)C1=CC=CC=C1 NPUXORBZRBIOMQ-RUZDIDTESA-N 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
- 150000004056 anthraquinones Chemical class 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
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- 230000008859 change Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001142 circular dichroism spectrum Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
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- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Substances CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 238000003487 electrochemical reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 230000002687 intercalation Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 150000002791 naphthoquinones Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000009781 safety test method Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- YZHUMGUJCQRKBT-UHFFFAOYSA-M sodium chlorate Chemical compound [Na+].[O-]Cl(=O)=O YZHUMGUJCQRKBT-UHFFFAOYSA-M 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
- POHWAQLZBIMPRN-UHFFFAOYSA-N tert-butyl n-(3-aminopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCN POHWAQLZBIMPRN-UHFFFAOYSA-N 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- GSQBIOQCECCMOQ-UHFFFAOYSA-N β-alanine ethyl ester Chemical compound CCOC(=O)CCN GSQBIOQCECCMOQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6816—Hybridisation assays characterised by the detection means
- C12Q1/6818—Hybridisation assays characterised by the detection means involving interaction of two or more labels, e.g. resonant energy transfer
Definitions
- Ligand for detecting electrochemically active sequence-specific double-stranded nucleic acid molecules Ligand for detecting electrochemically active sequence-specific double-stranded nucleic acid molecules
- the present invention relates to an electrochemically active Felucene compound and the like which can be used as a ligand for detecting a sequence-specific double-stranded nucleic acid molecule.
- the DNA microarray (DNA chip) is used for slide glass or silicon printing.
- RNA or DNA sample is hybridized, and the transcription amount of each gene is measured by using the intensity of the I-prepriding format as an index.
- DNA microarrays are also being used for detecting single nucleotide polymorphisms (SNPs).
- DNA chips include an “affimetrix type” sold by Affimetrix Inc. in the United States and a “Stamford type” developed by Stanford University in the United States.
- Amorphous type chips use a semiconductor processing technology to synthesize DNA probes at a high density on a silicon substrate.Thousands to tens of thousands of probes are fixed on one chip. You can do it.
- Stanford-type chips are made by dropping a prepared DNA fragment onto a slide. In these chips, detection is generally performed by image analysis using a fluorescent dye bound to a target.
- electrochemi cal Ar ray ECA chip
- electrochemi cal Ar ray ECA chip
- the electrochemical detection of such hybridization is carried out by using a conductive compound among compounds called "intercalating agents" having a property of being inserted between adjacent base pairs of double-stranded DNA. Done.
- conductive intercalating agents for example, many compounds such as anthraquinone, naphthoquinone, porphyrin, and phlegmene are already known. Examples have been reported (Fan, C .; Plaxco, KW; Heeger, AJ Proc. Natl.
- PIPA polyamide
- Patent Document 1 Japanese Patent Application Laid-Open No. 2003-300
- Patent Document 2 Japanese Patent Application Laid-Open No. 2003-83396
- Non-Patent Document 1 Fan, C .; Plaxco, K.W .; Heeger, A. J. Proc. Natl. Acad. Sci. USA, 2003, 100, 9134-9137.
- Non-Patent Document 2 Mrksich, M .; Parks, ME .; Derevan, P.B.J. Am. Chem. Soc. 1994, 116, 7983-7988.
- Non-Patent Document 3 Rucker, V.C .; Foister, S .; Melander, C .; Dervan, P.B.J. Am. Chem. Soc. 2003, 125, 1195-1202.
- Non-Patent Document 4 Wang, Y-D .; Dziegielewski, J .; Wurtz, N.R .; Dzielewska, B .; Dervan, P. B. Beerman, T.A. Nucleic Acids Res. 2003 31, 1208-1215.
- Non-Patent Document 5 Foister, S .; Marques, M.A .; Doss, R.M .; Dervan, P.B.Bioorganic Med. Chem. Lett. 2003, 11, 4333-4340
- Intercalation ij which has been used for conventional electrochemical DNA chips, binds not only to double-stranded DNA but also to single-stranded DNA, and generates electrical signals based on non-double-stranded DNA.
- the problem is that the noise current that is generated or generated by the free intercalating agent becomes the detection noise, and as a result, the detection sensitivity, that is, the electrochemical signal-to-noise ratio (S / N) is high. there were.
- the present inventor has proposed a compound capable of specifically recognizing the base sequence of a double-stranded (double-stranded) nucleic acid molecule by modifying a linker region in a pyrrole-imidazole 'polyamide structure.
- a compound having a phenoctene moiety in the linker region in the pyrrole-imidazole-polyamide structure we succeeded in synthesizing a compound having a phenoctene moiety in the linker region in the pyrrole-imidazole-polyamide structure, and solved the above problems.
- the present invention provides, as a first aspect, a ferrocene compound represented by the general formula (I):
- A is a divalent fluorene-containing linker or fluorene-1,1'-yl
- R represents a hydrogen atom or an alkyl
- n and m are arbitrary natural numbers.
- V and X are the following general formulas (II) or (II-11):
- U represents a nitrogen atom, methine, or hydroxymethine
- Z is a general formula (IV) or (V):
- the bond on the 1,1′-yl side of the phenylene-containing linker or phenylene group of V 1 is (1-C0—NR 2 —), and other V n and Both ends of Xm are related to (-CO— NH—) bond.
- the compound of the present invention represented by the above general formula (I) is composed of a divalent phenol-containing linker and two pyro-imidazole polyamide (PIPA) regions bonded thereto.
- the fluorene-containing linker may have any structure as long as it is a compound (atomic group) that contains the fluorene group and can exert the above-mentioned functions.
- n and m are preferably natural numbers in the range of 3 to 20, more preferably 3 to 10, and the imidazole derivative and the pyrrole derivative in the atomic group linked to both ends of the phenoctene-containing linker of the compound of the present invention.
- n is one less than m so that the total number of derivatives is finally equal.
- divalent phenol-containing linker (A) examples include the following general formula (V I).
- R and R 3 represent a hydrogen atom or alkyl, and j and k represent the same or different integers from 0 to 5).
- R 2 and R 3 are preferably an alkyl group having one to several carbon atoms, such as a methyl group.
- the compound of the present invention can be synthesized, for example, by the steps shown in the following Examples. Various reaction conditions and the like not specifically described in the present specification can be easily selected and adopted by those skilled in the art.
- the present invention provides, as a second aspect, a process for producing the compound of the present invention, which comprises a process comprising a condensation reaction with methyl feneopene methyldicarboxylate, methylaminophenoxymethylcarboxylate, or fengopenic acid carboxylic acid as a starting material.
- a process for producing the compound of the present invention comprises a condensation reaction with methyl feneopene methyldicarboxylate, methylaminophenoxymethylcarboxylate, or fengopenic acid carboxylic acid as a starting material.
- Method One specific example is shown in the following reaction schemes of Chemical Formulas 16 to 21 in the present specification, and includes a production method comprising the steps specifically described in Examples.
- the present invention relates to a ligand for sequence-specific detection of a double-stranded nucleic acid molecule comprising the Fehuasin compound of the present invention.
- the present invention provides, as a fourth aspect, the use of a double-stranded nucleic acid molecule electrochemically characterized by using a compound capable of binding sequence-specifically to a double-stranded nucleic acid molecule.
- the present invention relates to a detection method and an electrochemical detection device or instrument. The invention's effect
- an electrochemical signal-to-noise ratio in electrochemical detection can be improved.
- (S / N) can be reduced, and as a result, detection sensitivity and (accuracy) can be greatly improved, and quantitative measurement of ultra-trace amounts of nucleic acid molecules is enabled.
- FIG. 1 is a CD profile obtained by titration of 15-mer DNA obtained in Example 2. The reaction was carried out with 10 mM sodium codylate (pH 6.9) containing 10 mM KC1, 10 mg Cl 2, 5 mM CaCl 2 .
- FIG. 2 is a CD profile of titration of 11-mer DNA obtained in Example 5.
- FIG. 3 shows the electrochemical characteristics of the compound of the present invention obtained in the test of Example 6 by cyclic voltammetry (CV). Test, using the present invention compound (5 mM), 0.2 NaC10 4 containing New, measured in ⁇ - dimethylformamide ⁇ bromide.
- nucleic acid means DNA and RNA, and therefore, double-stranded nucleic acid molecules include DNA-DNA and DNA-RNA.
- nucleic acid molecule of the sample one evening
- mRNA and cDNA prepared by reverse transcription reaction or a fragment thereof can be used.
- a nucleic acid molecule used as a probe cDNA or a fragment thereof, a synthetic oligonucleotide, or the like can be used. These vary depending on the type of electrochemical detection method or device, etc. Is a well-known technical matter.
- a G / C base pair and an A / T (U) pair in a double-stranded nucleic acid molecule to be detected as a result of hybridization are represented by a general formula:
- the principle of measurement of the electrochemical detection method of the present invention is the hybridization between nucleic acid molecules, and can be carried out by any means and operation known to those skilled in the art.
- a method using hybridization on a solid phase a method using a DNA microarray (DNA chip) can be mentioned.
- a device or an instrument for example, an electrochemical chip or an ECA chip in which such an electrochemical detection method is performed is known to those skilled in the art, and such a device or an instrument can be used in the present invention. come.
- Such a device or apparatus can be easily prepared by a method well known to those skilled in the art.
- the detected electric signals include electric signals such as electric current, electric conductivity, electric potential, electric capacity, inductance, impedance, etc., such as cyclic voltage (CV) and differential pulse voltammetry. It is measured by an instrument such as a tree (DPV), linear sweep voltammography, and a potentiostat.
- electric signals such as electric current, electric conductivity, electric potential, electric capacity, inductance, impedance, etc.
- CV cyclic voltage
- DUV linear sweep voltammography
- potentiostat a potentiostat
- the method for electrochemically detecting a sequence-specific double-stranded nucleic acid molecule using the ligand for sequence-specific detection of a double-stranded nucleic acid molecule of the present invention includes polymorphism analysis such as single nucleotide polymorphism (SNP), It can be used for various measurements based on hybridization of nucleic acid molecules, such as determination, gene mutation analysis, and gene expression monitoring.
- SNP single nucleotide polymorphism
- This compound was synthesized according to the following reaction scheme.
- the structure of this compound was designed in consideration of both the availability of starting materials and the chemical stability of products and intermediates.
- the sequence of the PIPA region aims to bind to a CGC / GCG sequence targeting a single nucleotide mutation in the human genome that may be a factor in determining interferon resistance in patients infected with hepatitis C virus. was designed.
- Methyl fendicarboxylate (2) is a chloride of 2-q- 1-methylpyridinium (CMPI) (Bald, E ,; Saigo, K .; Mukaiyama, T. Chem. Lett. 1975, 1163) -1166) to condense with N-t-butoxycarbonyl-1,3-propandiamine to obtain a yield of 87%.
- CMPI 2-q- 1-methylpyridinium
- the resulting compound (3) was treated with an alkaline aqueous solution to be converted to a carboxylic acid (4). This was condensed with ethyl 3-aminopropionate to obtain a phenol-coupled unit (5) (yield: 62%).
- compound 8 (187.61119, 0.477111 [1101]) was dissolved in methylene chloride (4,771111), and diisopropylethylamine (0.162 ml, 0.947 mmol) and 0- (benzotriazolyl-yl)- ⁇ , ⁇ , ⁇ ', ⁇ '-Tetramethylperonium hexafluorofluorophosphate (361.8 (119, 0.954 maraudal 01)) was added as a condensing agent (Dourtoglou, V .; Ziegler, J.-C. Gross, B.
- FIG. 1 is the CD profile of the above titration of DNA with 0, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2 and 1.4 equivalents of the compound.
- the compound of the present invention was further synthesized according to the following reaction scheme.
- the white powder precipitated in the system was separated by filtration, washed with water, the organic layer was recovered, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified using silica gel chromatography to obtain 25a (2.52 g, 82%) o
- Example 2 the binding of the above compound to the target DNA (5 ′ GACTGCGTAGG 3, / 3 ′ CTGACGCATCC 5 ′) was examined for the purpose of confirming the usefulness of the above compound as a ligand for double-stranded DNA. Inspected by vector. The results are shown in FIG. It is a CD profile of the above-mentioned titration of DNA with this compound. Elliptical polarization at 300-360 nm is induced by the minor groove coupling. (Pilch, DS; Poklar, N .; Baird, E.E .; Dervan, P.B .; Breslauer, III. J. Biochemistry 1999, 38, 2143-2151.).
- Example 6 Measurement of electrochemical properties by cyclic portometry (CV)
- Figure 3 shows the results of examining the electrochemical properties of the above compounds (1a and 3) by using CV. This result indicates that the present compound has the activity of the electrochemical reaction caused by the oxidation of the phenoctene moiety.
- Industrial applicability The present invention has application in a wide range of industries, including drug discovery, clinical testing, drug screening, chemical safety testing, food testing, quarantine, forensic testing, brewing, agriculture, forestry, fisheries, and animal husbandry. You can do it.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Description
Claims
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US10/590,232 US7863455B2 (en) | 2004-02-24 | 2005-02-23 | Electrochemically active ligand for sequence-specific detection of double-stranded nucleic acid molecule |
JP2006510910A JP5006033B2 (ja) | 2004-02-24 | 2005-02-23 | 電気化学的に活性な配列特異的二本鎖核酸分子検出用リガンド |
EP05719755A EP1719777A4 (en) | 2004-02-24 | 2005-02-23 | LIGAND WITH ELECTROCHEMICAL ACTIVITY FOR THE SPECIFIC DETECTION OF DOUBLE STRANDED NUCLEIC ACID MOLECULE SEQUENCE |
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JP2004-47605 | 2004-02-24 | ||
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WO2005087784A1 true WO2005087784A1 (ja) | 2005-09-22 |
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EP (1) | EP1719777A4 (ja) |
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JP2003000300A (ja) | 2001-06-19 | 2003-01-07 | Mitsubishi Heavy Ind Ltd | Dnaチップを用いた塩基配列決定又は核酸定量方法 |
JP2003083968A (ja) | 2001-09-14 | 2003-03-19 | Jsr Corp | Dnaチップおよびアッセイ方法 |
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JP2967197B1 (ja) * | 1998-08-11 | 1999-10-25 | 九州大学長 | 遺伝子の特殊一本鎖核酸部位の検出用プローブ、遺伝子の特殊一本鎖核酸部位の検出方法およびその装置 |
CA2351479A1 (en) * | 1998-11-19 | 2000-06-02 | Bio Merieux | Electrically conductive electroactive functionalized conjugated polymers, and uses thereof |
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2005
- 2005-02-23 WO PCT/JP2005/003440 patent/WO2005087784A1/ja active Application Filing
- 2005-02-23 US US10/590,232 patent/US7863455B2/en not_active Expired - Fee Related
- 2005-02-23 JP JP2006510910A patent/JP5006033B2/ja not_active Expired - Fee Related
- 2005-02-23 EP EP05719755A patent/EP1719777A4/en not_active Withdrawn
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WO2017061128A1 (ja) * | 2015-10-08 | 2017-04-13 | 凸版印刷株式会社 | ピロールイミダゾール含有ポリアミドを用いた標的二本鎖核酸分子の濃縮方法およびキット |
Also Published As
Publication number | Publication date |
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EP1719777A1 (en) | 2006-11-08 |
JPWO2005087784A1 (ja) | 2008-01-24 |
EP1719777A4 (en) | 2009-07-29 |
JP5006033B2 (ja) | 2012-08-22 |
US7863455B2 (en) | 2011-01-04 |
US20070172826A1 (en) | 2007-07-26 |
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