JPH10509740A - カチオン性オリゴヌクレオチド、ならびに関連の合成および使用の方法 - Google Patents
カチオン性オリゴヌクレオチド、ならびに関連の合成および使用の方法Info
- Publication number
- JPH10509740A JPH10509740A JP9508693A JP50869397A JPH10509740A JP H10509740 A JPH10509740 A JP H10509740A JP 9508693 A JP9508693 A JP 9508693A JP 50869397 A JP50869397 A JP 50869397A JP H10509740 A JPH10509740 A JP H10509740A
- Authority
- JP
- Japan
- Prior art keywords
- group
- alkyl
- cationic
- independently selected
- bond
- 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.)
- Expired - Lifetime
Links
- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 116
- 125000002091 cationic group Chemical group 0.000 title claims abstract description 100
- 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 title claims abstract description 76
- 238000000034 method Methods 0.000 title claims abstract description 29
- 230000015572 biosynthetic process Effects 0.000 title description 20
- 238000003786 synthesis reaction Methods 0.000 title description 11
- 229910052698 phosphorus Inorganic materials 0.000 claims abstract description 29
- 125000000129 anionic group Chemical group 0.000 claims abstract description 23
- 125000004437 phosphorous atom Chemical group 0.000 claims abstract description 21
- 238000007899 nucleic acid hybridization Methods 0.000 claims abstract description 15
- 238000003556 assay Methods 0.000 claims abstract description 14
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 48
- 229910052717 sulfur Inorganic materials 0.000 claims description 46
- -1 phospho Chemical class 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 26
- 102000039446 nucleic acids Human genes 0.000 claims description 26
- 108020004707 nucleic acids Proteins 0.000 claims description 26
- 150000007523 nucleic acids Chemical class 0.000 claims description 26
- 239000002777 nucleoside Substances 0.000 claims description 19
- 239000000523 sample Substances 0.000 claims description 19
- 125000003729 nucleotide group Chemical group 0.000 claims description 18
- 239000002773 nucleotide Substances 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000000732 arylene group Chemical group 0.000 claims description 10
- 229910052711 selenium Inorganic materials 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 9
- 150000008300 phosphoramidites Chemical class 0.000 claims description 6
- 238000010898 silica gel chromatography Methods 0.000 claims description 5
- 108020005187 Oligonucleotide Probes Proteins 0.000 claims description 4
- 239000012491 analyte Substances 0.000 claims description 4
- 239000002751 oligonucleotide probe Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 230000000692 anti-sense effect Effects 0.000 abstract description 12
- 150000001875 compounds Chemical class 0.000 abstract description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 74
- 239000011780 sodium chloride Substances 0.000 description 39
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 24
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 23
- 150000003839 salts Chemical class 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
- 230000007704 transition Effects 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 20
- 108020004414 DNA Proteins 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 14
- 238000010828 elution Methods 0.000 description 14
- 239000000539 dimer Substances 0.000 description 13
- 238000009396 hybridization Methods 0.000 description 13
- 238000004679 31P NMR spectroscopy Methods 0.000 description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 12
- 238000004809 thin layer chromatography Methods 0.000 description 12
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 10
- 150000004713 phosphodiesters Chemical class 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 238000001228 spectrum Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 108091034057 RNA (poly(A)) Proteins 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 102000053602 DNA Human genes 0.000 description 7
- 125000002947 alkylene group Chemical group 0.000 description 7
- 239000011574 phosphorus Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 6
- 238000010494 dissociation reaction Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 235000000346 sugar Nutrition 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- 229940104230 thymidine Drugs 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 5
- 238000001142 circular dichroism spectrum Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 230000005593 dissociations Effects 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 150000003833 nucleoside derivatives Chemical class 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 108091033319 polynucleotide Proteins 0.000 description 5
- 102000040430 polynucleotide Human genes 0.000 description 5
- 239000002157 polynucleotide Substances 0.000 description 5
- 238000004007 reversed phase HPLC Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- SXUXMRMBWZCMEN-ZOQUXTDFSA-N 2'-O-methyluridine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 SXUXMRMBWZCMEN-ZOQUXTDFSA-N 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 101710163270 Nuclease Proteins 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 4
- 238000007323 disproportionation reaction Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical group 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 125000003835 nucleoside group Chemical group 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 150000003230 pyrimidines Chemical class 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- SXUXMRMBWZCMEN-UHFFFAOYSA-N 2'-O-methyl uridine Natural products COC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 SXUXMRMBWZCMEN-UHFFFAOYSA-N 0.000 description 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 125000004450 alkenylene group Chemical group 0.000 description 3
- 125000004419 alkynylene group Chemical group 0.000 description 3
- 230000001588 bifunctional effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 150000003212 purines Chemical class 0.000 description 3
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 3
- 239000012266 salt solution Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 238000010532 solid phase synthesis reaction Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 150000003536 tetrazoles Chemical class 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000012069 chiral reagent Substances 0.000 description 2
- 230000009918 complex formation Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 238000002515 oligonucleotide synthesis Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- SXADIBFZNXBEGI-UHFFFAOYSA-N phosphoramidous acid Chemical class NP(O)O SXADIBFZNXBEGI-UHFFFAOYSA-N 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QQVDJLLNRSOCEL-UHFFFAOYSA-N (2-aminoethyl)phosphonic acid Chemical compound [NH3+]CCP(O)([O-])=O QQVDJLLNRSOCEL-UHFFFAOYSA-N 0.000 description 1
- KFYRJJBUHYILSO-YFKPBYRVSA-N (2s)-2-amino-3-dimethylarsanylsulfanyl-3-methylbutanoic acid Chemical compound C[As](C)SC(C)(C)[C@@H](N)C(O)=O KFYRJJBUHYILSO-YFKPBYRVSA-N 0.000 description 1
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 1
- VKIGAWAEXPTIOL-UHFFFAOYSA-N 2-hydroxyhexanenitrile Chemical compound CCCCC(O)C#N VKIGAWAEXPTIOL-UHFFFAOYSA-N 0.000 description 1
- 125000004810 2-methylpropylene group Chemical group [H]C([H])([H])C([H])(C([H])([H])[*:2])C([H])([H])[*:1] 0.000 description 1
- 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
- 229940105325 3-dimethylaminopropylamine Drugs 0.000 description 1
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 229930182476 C-glycoside Natural products 0.000 description 1
- 150000000700 C-glycosides Chemical class 0.000 description 1
- METVIZHTDMPZPL-UHFFFAOYSA-N COOP(N)(O)=O Chemical compound COOP(N)(O)=O METVIZHTDMPZPL-UHFFFAOYSA-N 0.000 description 1
- QCMYYKRYFNMIEC-UHFFFAOYSA-N COP(O)=O Chemical class COP(O)=O QCMYYKRYFNMIEC-UHFFFAOYSA-N 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 1
- 101100050026 Enterobacteria phage T4 y01J gene Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 229930182474 N-glycoside Natural products 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000002547 anomalous effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000003139 biocide Substances 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000003196 chaotropic effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 238000002983 circular dichroism Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- GYOZYWVXFNDGLU-XLPZGREQSA-N dTMP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 GYOZYWVXFNDGLU-XLPZGREQSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000006642 detritylation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical group O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000000215 hyperchromic effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000003367 kinetic assay Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-L methylphosphonate(2-) Chemical compound CP([O-])([O-])=O YACKEPLHDIMKIO-UHFFFAOYSA-L 0.000 description 1
- 230000037230 mobility Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- 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
-
- 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
- C12Q1/6839—Triple helix formation or other higher order conformations in hybridisation assays
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US190195P | 1995-08-04 | 1995-08-04 | |
| US60/001,901 | 1995-08-04 | ||
| US08/693,831 | 1996-07-31 | ||
| US08/693,831 US6017700A (en) | 1995-08-04 | 1996-07-31 | Cationic oligonucleotides, and related methods of synthesis and use |
| PCT/US1996/013056 WO1997006183A1 (en) | 1995-08-04 | 1996-08-01 | Cationic oligonucleotides, and related methods of synthesis and use |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007208670A Division JP2008013571A (ja) | 1995-08-04 | 2007-08-09 | カチオン性オリゴヌクレオチド、ならびに関連の合成および使用の方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH10509740A true JPH10509740A (ja) | 1998-09-22 |
| JPH10509740A5 JPH10509740A5 (cg-RX-API-DMAC7.html) | 2004-09-09 |
Family
ID=26669648
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9508693A Expired - Lifetime JPH10509740A (ja) | 1995-08-04 | 1996-08-01 | カチオン性オリゴヌクレオチド、ならびに関連の合成および使用の方法 |
| JP2007208670A Pending JP2008013571A (ja) | 1995-08-04 | 2007-08-09 | カチオン性オリゴヌクレオチド、ならびに関連の合成および使用の方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007208670A Pending JP2008013571A (ja) | 1995-08-04 | 2007-08-09 | カチオン性オリゴヌクレオチド、ならびに関連の合成および使用の方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US6017700A (cg-RX-API-DMAC7.html) |
| EP (1) | EP0785942A1 (cg-RX-API-DMAC7.html) |
| JP (2) | JPH10509740A (cg-RX-API-DMAC7.html) |
| AU (1) | AU702309B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2201963A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO1997006183A1 (cg-RX-API-DMAC7.html) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005200405A (ja) * | 2003-12-02 | 2005-07-28 | F Hoffmann La Roche Ag | 分子ロッドを含むオリゴヌクレオチド |
| JP2009543783A (ja) * | 2006-07-12 | 2009-12-10 | ザ レジェンツ オブ ザ ユニヴァースティ オブ カリフォルニア | 可逆的なホスホトリエステル電荷中和保護基による核酸の形質導入可能な送達 |
| JP2015528002A (ja) * | 2012-07-13 | 2015-09-24 | ウェイブ ライフ サイエンス プライベート リミテッド | キラル制御 |
| WO2022230990A1 (ja) * | 2021-04-28 | 2022-11-03 | 国立研究開発法人科学技術振興機構 | 人工核酸及びそれを用いた核酸の送達方法 |
| US11597744B2 (en) | 2017-06-30 | 2023-03-07 | Sirius Therapeutics, Inc. | Chiral phosphoramidite auxiliaries and methods of their use |
| US11981703B2 (en) | 2016-08-17 | 2024-05-14 | Sirius Therapeutics, Inc. | Polynucleotide constructs |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2436857A1 (en) * | 2000-12-14 | 2002-06-20 | Gen-Probe Incorporated | Method and kit for enhancing the association rates of polynucleotides |
| CN102282155B (zh) | 2008-12-02 | 2017-06-09 | 日本波涛生命科学公司 | 磷原子修饰的核酸的合成方法 |
| BR112012000828A8 (pt) | 2009-07-06 | 2017-10-10 | Ontorii Inc | Novas pró-drogas de ácido nucleico e métodos de uso das mesmas |
| EP2620428B1 (en) | 2010-09-24 | 2019-05-22 | Wave Life Sciences Ltd. | Asymmetric auxiliary group |
| CA2834665C (en) * | 2011-05-10 | 2019-08-20 | Bonac Corporation | Process for preparing phosphate compound bearing isotope |
| ES2626488T3 (es) | 2011-07-19 | 2017-07-25 | Wave Life Sciences Pte. Ltd. | Procedimientos para la síntesis de ácidos nucleicos funcionalizados |
| BR112015000723A2 (pt) | 2012-07-13 | 2017-06-27 | Shin Nippon Biomedical Laboratories Ltd | adjuvante de ácido nucléico quiral |
| ES2862073T3 (es) | 2012-07-13 | 2021-10-06 | Wave Life Sciences Ltd | Grupo auxiliar asimétrico |
| CN104781271B (zh) | 2012-08-20 | 2018-07-06 | 加利福尼亚大学董事会 | 具有生物可逆的基团的多核苷酸 |
| EP3013964B1 (en) | 2013-06-28 | 2020-05-06 | ethris GmbH | Compositions for introducing rna into cells |
| US9410172B2 (en) | 2013-09-16 | 2016-08-09 | General Electric Company | Isothermal amplification using oligocation-conjugated primer sequences |
| WO2015108047A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
| JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| US10322173B2 (en) | 2014-01-15 | 2019-06-18 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
| CN113278617A (zh) | 2014-01-16 | 2021-08-20 | 波涛生命科学有限公司 | 手性设计 |
| JP2017507946A (ja) | 2014-02-26 | 2017-03-23 | エスリス ゲーエムベーハーｅｔｈｒｉｓ ＧｍｂＨ | Ｒｎａを胃腸内投与するための組成物 |
| EP3034539A1 (en) | 2014-12-19 | 2016-06-22 | Ethris GmbH | Compositions for introducing nucleic acid into cells |
| WO2018189382A1 (en) | 2017-04-14 | 2018-10-18 | Solstice Biologics, Ltd. | Immunomodulating polynucleotides, antibody conjugates thereof, and methods of their use |
| JP7256824B2 (ja) | 2018-04-25 | 2023-04-12 | エスリス ゲーエムベーハー | 粒子状製剤用の凍結保護剤 |
| JP2024507394A (ja) | 2021-02-26 | 2024-02-19 | エスリス ゲーエムベーハー | エアロゾル形成用の製剤および核酸を送達するためのエアロゾル |
| EP4327829A1 (en) | 2022-08-26 | 2024-02-28 | Ethris GmbH | Stabilization of lipid or lipidoid nanoparticle suspensions |
| JP2025529925A (ja) | 2022-08-26 | 2025-09-09 | エスリス ゲーエムベーハー | 安定な脂質またはリピドイドナノ粒子懸濁液 |
| WO2025045767A1 (en) | 2023-08-25 | 2025-03-06 | Ethris Gmbh | Stabilized lipid and lipidoid nanoparticle formulations with specific surfactant properties for enhanced pharmaceutical applications |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2586704B1 (fr) * | 1985-09-04 | 1987-12-18 | Centre Nat Rech Scient | Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation et a un groupe chimique activable, leur synthese et leurs applications a titre de nucleases artificielles specifiques de sequences. centre national de la recherche scientifique (cnrs) |
| US4868105A (en) * | 1985-12-11 | 1989-09-19 | Chiron Corporation | Solution phase nucleic acid sandwich assay |
| DE3916871A1 (de) * | 1989-05-24 | 1990-11-29 | Boehringer Mannheim Gmbh | Modifiziertes phosphoramidit-verfahren zur herstellung von modifizierten nukleinsaeuren |
| US4958013A (en) * | 1989-06-06 | 1990-09-18 | Northwestern University | Cholesteryl modified oligonucleotides |
| JPH07501542A (ja) * | 1991-11-25 | 1995-02-16 | ファーマジェニックス，インコーポレーテッド | アミノ炭化水素ホスホン酸塩成分を有するオリゴヌクレオチド |
-
1996
- 1996-07-31 US US08/693,831 patent/US6017700A/en not_active Expired - Lifetime
- 1996-08-01 EP EP96929675A patent/EP0785942A1/en not_active Withdrawn
- 1996-08-01 JP JP9508693A patent/JPH10509740A/ja not_active Expired - Lifetime
- 1996-08-01 WO PCT/US1996/013056 patent/WO1997006183A1/en not_active Ceased
- 1996-08-01 CA CA002201963A patent/CA2201963A1/en not_active Abandoned
- 1996-08-01 AU AU68971/96A patent/AU702309B2/en not_active Ceased
-
2007
- 2007-08-09 JP JP2007208670A patent/JP2008013571A/ja active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005200405A (ja) * | 2003-12-02 | 2005-07-28 | F Hoffmann La Roche Ag | 分子ロッドを含むオリゴヌクレオチド |
| JP2009543783A (ja) * | 2006-07-12 | 2009-12-10 | ザ レジェンツ オブ ザ ユニヴァースティ オブ カリフォルニア | 可逆的なホスホトリエステル電荷中和保護基による核酸の形質導入可能な送達 |
| JP2015062421A (ja) * | 2006-07-12 | 2015-04-09 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 可逆的なホスホトリエステル電荷中和保護基による核酸の形質導入可能な送達 |
| JP2015528002A (ja) * | 2012-07-13 | 2015-09-24 | ウェイブ ライフ サイエンス プライベート リミテッド | キラル制御 |
| JP2019069971A (ja) * | 2012-07-13 | 2019-05-09 | ウェイブ ライフ サイエンシズ リミテッドＷａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｌｔｄ． | キラル制御 |
| US11981703B2 (en) | 2016-08-17 | 2024-05-14 | Sirius Therapeutics, Inc. | Polynucleotide constructs |
| US11597744B2 (en) | 2017-06-30 | 2023-03-07 | Sirius Therapeutics, Inc. | Chiral phosphoramidite auxiliaries and methods of their use |
| WO2022230990A1 (ja) * | 2021-04-28 | 2022-11-03 | 国立研究開発法人科学技術振興機構 | 人工核酸及びそれを用いた核酸の送達方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| US6017700A (en) | 2000-01-25 |
| JP2008013571A (ja) | 2008-01-24 |
| EP0785942A1 (en) | 1997-07-30 |
| CA2201963A1 (en) | 1997-02-20 |
| AU6897196A (en) | 1997-03-05 |
| AU702309B2 (en) | 1999-02-18 |
| WO1997006183A1 (en) | 1997-02-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH10509740A (ja) | カチオン性オリゴヌクレオチド、ならびに関連の合成および使用の方法 | |
| Mag et al. | Synthesis and selective cleavage of oligodeoxyribonucleotldes containing non-chiral intemucieotlde phosphoramidate linkages | |
| JP6038860B2 (ja) | リン原子修飾核酸の合成方法 | |
| KR101032008B1 (ko) | 폴리뉴클레오티드 표지 시약 | |
| US20080064867A1 (en) | Process for the synthesis of oligonucleotides | |
| JPH0631305B2 (ja) | ヌクレオシド誘導体 | |
| JP5812478B2 (ja) | 抗癌剤結合性核酸アプタマー及びその利用 | |
| PT739898E (pt) | Mono-esteres de acidos fosfonucleicos processo para a sua preparacao e sua utilizacao | |
| CN114763367B (zh) | 化合物、缀合物及其用途 | |
| JP2000500158A (ja) | ユニバーサルな固体支持体およびその使用方法 | |
| CN112759620A (zh) | 肝靶向化合物及寡核苷酸缀合物 | |
| EP0611075B1 (en) | Modified oligodeoxyribonucleotides, their preparation and their therapeutic use | |
| HK1000191B (en) | Modified oligodeoxyribonucleotides, their preparation and their therapeutic use | |
| KR20080083668A (ko) | 광절단가능한 링커를 사용한 올리고뉴클레오티드의 합성 | |
| EP0358657B1 (en) | Poly(deoxyribonucleotides), pharmaceutical compositions, use and preparation of the poly(deoxyribonucleotides) | |
| NZ292140A (en) | Oligomers consisting of 1,5-anhydrohexitol nucleosides, antisence techniques. | |
| Ramzaeva et al. | Oligonucleotides Functionalized by Fluorescein and Rhodamine Dyes: Michael Addition of Methyl Acrylate to 2′‐Deoxypseudouridine | |
| US12150997B1 (en) | Compound, a conjugate and uses thereof | |
| JPH05501418A (ja) | オリゴヌクレオチドの官能化方法 | |
| JP4305966B2 (ja) | 光学活性なホスホン酸ジエステル結合を持つｄｎａプローブ | |
| US20020103365A1 (en) | Process for the synthesis of nucleic acids on a solid support and compounds which are useful in particular as solid supports in the said process | |
| AU2023202951A1 (en) | A compound, a conjugate and uses thereof | |
| CN117412983A (zh) | 包含硫代磷酸酯及硼烷磷酸酯的嵌合型核酸低聚物及其制造方法 | |
| JPH07121954B2 (ja) | アミノ−誘導化重合体を合成するための有機リン結合剤 | |
| HK1126183B (en) | Polynucleotide labelling reagent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070515 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070809 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20071106 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20081112 Year of fee payment: 9 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080229 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20080409 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20080529 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20080612 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20091112 Year of fee payment: 10 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101112 Year of fee payment: 11 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111112 Year of fee payment: 12 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121112 Year of fee payment: 13 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131112 Year of fee payment: 14 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| EXPY | Cancellation because of completion of term |