JP2007521813A5 - - Google Patents
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- Publication number
- JP2007521813A5 JP2007521813A5 JP2006551815A JP2006551815A JP2007521813A5 JP 2007521813 A5 JP2007521813 A5 JP 2007521813A5 JP 2006551815 A JP2006551815 A JP 2006551815A JP 2006551815 A JP2006551815 A JP 2006551815A JP 2007521813 A5 JP2007521813 A5 JP 2007521813A5
- Authority
- JP
- Japan
- Prior art keywords
- rna
- seq
- oligonucleotide
- ligand
- hybridization
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 55
- 108091034117 Oligonucleotide Proteins 0.000 claims description 49
- 238000009396 hybridization Methods 0.000 claims description 27
- 230000000694 effects Effects 0.000 claims description 26
- 108010002350 Interleukin-2 Proteins 0.000 claims description 25
- 238000003556 assay Methods 0.000 claims description 25
- 239000003446 ligand Substances 0.000 claims description 22
- 108020004999 messenger RNA Proteins 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 22
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 21
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 21
- 230000009471 action Effects 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 10
- 230000014509 gene expression Effects 0.000 claims description 9
- 108090000623 proteins and genes Proteins 0.000 claims description 9
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 6
- 230000003993 interaction Effects 0.000 claims description 6
- 230000001105 regulatory effect Effects 0.000 claims description 5
- 108020004707 nucleic acids Proteins 0.000 claims description 4
- 102000039446 nucleic acids Human genes 0.000 claims description 4
- 150000007523 nucleic acids Chemical class 0.000 claims description 4
- 238000006384 oligomerization reaction Methods 0.000 claims description 4
- 108020004414 DNA Proteins 0.000 claims description 3
- 230000008859 change Effects 0.000 claims description 3
- 102000053602 DNA Human genes 0.000 claims description 2
- 230000026279 RNA modification Effects 0.000 claims description 2
- 230000000295 complement effect Effects 0.000 claims description 2
- 238000013519 translation Methods 0.000 claims description 2
- 102000000588 Interleukin-2 Human genes 0.000 claims 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 108091093037 Peptide nucleic acid Proteins 0.000 claims 1
- 230000014632 RNA localization Effects 0.000 claims 1
- 238000007385 chemical modification Methods 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 238000013537 high throughput screening Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 108700015856 ELAV-Like Protein 1 Proteins 0.000 description 39
- 108020005345 3' Untranslated Regions Proteins 0.000 description 31
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 16
- 238000005259 measurement Methods 0.000 description 14
- 238000010494 dissociation reaction Methods 0.000 description 10
- 230000005593 dissociations Effects 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 9
- 239000013642 negative control Substances 0.000 description 8
- 238000001514 detection method Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 101150063790 orn gene Proteins 0.000 description 5
- 230000010287 polarization Effects 0.000 description 5
- 238000004007 reversed phase HPLC Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 229920001992 poloxamer 407 Polymers 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000001506 fluorescence spectroscopy Methods 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 238000002523 gelfiltration Methods 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000008707 rearrangement Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229920002101 Chitin Polymers 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 238000004847 absorption spectroscopy Methods 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000009918 complex formation Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- -1 nucleotide phosphoramidite Chemical class 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 229940006193 2-mercaptoethanesulfonic acid Drugs 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108091032955 Bacterial small RNA Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 101000925870 Homo sapiens ELAV-like protein 1 Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000012436 analytical size exclusion chromatography Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000001142 circular dichroism spectrum Methods 0.000 description 1
- ZNEWHQLOPFWXOF-UHFFFAOYSA-N coenzyme M Chemical compound OS(=O)(=O)CCS ZNEWHQLOPFWXOF-UHFFFAOYSA-N 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000000198 fluorescence anisotropy Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000017730 intein-mediated protein splicing Effects 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 238000005192 partition 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
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000012536 storage buffer Substances 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US54231504P | 2004-02-05 | 2004-02-05 | |
| US56046404P | 2004-04-08 | 2004-04-08 | |
| PCT/EP2005/001168 WO2005075637A2 (en) | 2004-02-05 | 2005-02-04 | Screening assays |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007521813A JP2007521813A (ja) | 2007-08-09 |
| JP2007521813A5 true JP2007521813A5 (https=) | 2008-03-21 |
Family
ID=34841137
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006551815A Pending JP2007521813A (ja) | 2004-02-05 | 2005-02-04 | スクリーニングアッセイ |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1713913A2 (https=) |
| JP (1) | JP2007521813A (https=) |
| KR (1) | KR20060135798A (https=) |
| CN (1) | CN1918294A (https=) |
| AU (2) | AU2005210006B2 (https=) |
| BR (1) | BRPI0507480A (https=) |
| CA (1) | CA2554218A1 (https=) |
| IL (1) | IL176991A0 (https=) |
| RU (1) | RU2006131550A (https=) |
| WO (1) | WO2005075637A2 (https=) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011062166A1 (ja) * | 2009-11-17 | 2011-05-26 | 武田薬品工業株式会社 | Rnaの二次構造の動態を予測する方法 |
| JP2013519869A (ja) | 2010-02-10 | 2013-05-30 | ノバルティス アーゲー | 筋肉成長のための方法および化合物 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004099411A1 (en) * | 2003-05-07 | 2004-11-18 | Novartis Ag | A method for dissecting the rna secondary structure dependence of rna-ligand interactions |
-
2005
- 2005-02-04 RU RU2006131550/13A patent/RU2006131550A/ru not_active Application Discontinuation
- 2005-02-04 AU AU2005210006A patent/AU2005210006B2/en not_active Ceased
- 2005-02-04 EP EP05701358A patent/EP1713913A2/en not_active Withdrawn
- 2005-02-04 CN CNA2005800042234A patent/CN1918294A/zh active Pending
- 2005-02-04 CA CA002554218A patent/CA2554218A1/en not_active Abandoned
- 2005-02-04 JP JP2006551815A patent/JP2007521813A/ja active Pending
- 2005-02-04 WO PCT/EP2005/001168 patent/WO2005075637A2/en not_active Ceased
- 2005-02-04 KR KR1020067017940A patent/KR20060135798A/ko not_active Withdrawn
- 2005-02-04 BR BRPI0507480-0A patent/BRPI0507480A/pt not_active IP Right Cessation
-
2006
- 2006-07-20 IL IL176991A patent/IL176991A0/en unknown
-
2008
- 2008-12-23 AU AU2008261191A patent/AU2008261191A1/en not_active Abandoned
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