DE3650699T2 - Immunotestmittel für Polynukleotid und Verfahren - Google Patents
Immunotestmittel für Polynukleotid und VerfahrenInfo
- Publication number
- DE3650699T2 DE3650699T2 DE3650699T DE3650699T DE3650699T2 DE 3650699 T2 DE3650699 T2 DE 3650699T2 DE 3650699 T DE3650699 T DE 3650699T DE 3650699 T DE3650699 T DE 3650699T DE 3650699 T2 DE3650699 T2 DE 3650699T2
- Authority
- DE
- Germany
- Prior art keywords
- polymer
- subunit
- subunits
- mmol
- backbone
- 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
- 108091033319 polynucleotide Proteins 0.000 title claims abstract description 70
- 102000040430 polynucleotide Human genes 0.000 title claims abstract description 70
- 239000002157 polynucleotide Substances 0.000 title claims abstract description 70
- 238000000034 method Methods 0.000 title description 127
- 238000003018 immunoassay Methods 0.000 title 1
- 229920000642 polymer Polymers 0.000 claims abstract description 226
- 230000000295 complement effect Effects 0.000 claims abstract description 29
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 27
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 17
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- MHCMWGPPLOSCJY-UHFFFAOYSA-N 4-$l^{1}-azanylmorpholine Chemical compound [N]N1CCOCC1 MHCMWGPPLOSCJY-UHFFFAOYSA-N 0.000 claims abstract description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000005859 coupling reaction Methods 0.000 claims description 68
- 238000010168 coupling process Methods 0.000 claims description 63
- 230000008878 coupling Effects 0.000 claims description 57
- 239000000203 mixture Substances 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
- 150000001412 amines Chemical class 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 claims description 8
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims description 5
- 239000012736 aqueous medium Substances 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 150000003212 purines Chemical class 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 93
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 239000012491 analyte Substances 0.000 description 84
- 239000002585 base Substances 0.000 description 79
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
- 239000000243 solution Substances 0.000 description 73
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 64
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 239000003153 chemical reaction reagent Substances 0.000 description 60
- 238000006243 chemical reaction Methods 0.000 description 56
- 230000027455 binding Effects 0.000 description 55
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- 239000002777 nucleoside Substances 0.000 description 43
- -1 purine-like Chemical compound 0.000 description 43
- 239000007787 solid Substances 0.000 description 43
- 239000000523 sample Substances 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- 239000000539 dimer Substances 0.000 description 38
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
- 239000002904 solvent Substances 0.000 description 34
- 230000015572 biosynthetic process Effects 0.000 description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
- 238000002360 preparation method Methods 0.000 description 31
- 125000006239 protecting group Chemical group 0.000 description 30
- 150000003833 nucleoside derivatives Chemical class 0.000 description 28
- 239000002253 acid Substances 0.000 description 27
- 238000000137 annealing Methods 0.000 description 27
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 25
- 125000004122 cyclic group Chemical group 0.000 description 24
- 239000012038 nucleophile Substances 0.000 description 22
- 150000003839 salts Chemical class 0.000 description 22
- 239000000741 silica gel Substances 0.000 description 22
- 229910002027 silica gel Inorganic materials 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 20
- 238000004587 chromatography analysis Methods 0.000 description 19
- 238000003786 synthesis reaction Methods 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- 239000000463 material Substances 0.000 description 18
- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- 102000039446 nucleic acids Human genes 0.000 description 18
- 108020004707 nucleic acids Proteins 0.000 description 18
- 150000007523 nucleic acids Chemical class 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 18
- 235000011152 sodium sulphate Nutrition 0.000 description 18
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 17
- 230000004913 activation Effects 0.000 description 17
- 239000000872 buffer Substances 0.000 description 17
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 16
- 125000006853 reporter group Chemical group 0.000 description 16
- 241000894007 species Species 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 125000002091 cationic group Chemical group 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 14
- 108091034117 Oligonucleotide Proteins 0.000 description 13
- 238000003556 assay Methods 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- 238000001514 detection method Methods 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- 125000005647 linker group Chemical group 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 229940029575 guanosine Drugs 0.000 description 11
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical group CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 11
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 10
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 10
- 239000011521 glass Substances 0.000 description 10
- 125000003835 nucleoside group Chemical group 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
- 125000003277 amino group Chemical group 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 239000002342 ribonucleoside Substances 0.000 description 9
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 8
- 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 8
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000003213 activating effect Effects 0.000 description 8
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 8
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 8
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- 230000035945 sensitivity Effects 0.000 description 8
- 125000006850 spacer group Chemical group 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 7
- ACBQROXDOHKANW-UHFFFAOYSA-N bis(4-nitrophenyl) carbonate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)OC1=CC=C([N+]([O-])=O)C=C1 ACBQROXDOHKANW-UHFFFAOYSA-N 0.000 description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
- 238000013461 design Methods 0.000 description 7
- 239000012039 electrophile Substances 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 230000000269 nucleophilic effect Effects 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 239000000908 ammonium hydroxide Substances 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
- 238000002405 diagnostic procedure Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- IRXSLJNXXZKURP-UHFFFAOYSA-N fluorenylmethyloxycarbonyl chloride Chemical compound C1=CC=C2C(COC(=O)Cl)C3=CC=CC=C3C2=C1 IRXSLJNXXZKURP-UHFFFAOYSA-N 0.000 description 6
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 150000004713 phosphodiesters Chemical class 0.000 description 6
- 229920000768 polyamine Polymers 0.000 description 6
- 238000002390 rotary evaporation Methods 0.000 description 6
- 239000002002 slurry Substances 0.000 description 6
- 239000007790 solid phase Substances 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 5
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 5
- SUTWPJHCRAITLU-UHFFFAOYSA-N 6-aminohexan-1-ol Chemical compound NCCCCCCO SUTWPJHCRAITLU-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 5
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000005549 deoxyribonucleoside Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 235000021317 phosphate Nutrition 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 5
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 4
- GKAVOHSJEWKJFB-UHFFFAOYSA-N 2-(benzenesulfonyl)ethyl carbonochloridate Chemical compound ClC(=O)OCCS(=O)(=O)C1=CC=CC=C1 GKAVOHSJEWKJFB-UHFFFAOYSA-N 0.000 description 4
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 4
- ZDTFMPXQUSBYRL-UUOKFMHZSA-N 2-Aminoadenosine Chemical compound C12=NC(N)=NC(N)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O ZDTFMPXQUSBYRL-UUOKFMHZSA-N 0.000 description 4
- AFXKCBFBGDUFAM-UHFFFAOYSA-N 2-methylpropan-2-amine;hydrofluoride Chemical compound [F-].CC(C)(C)[NH3+] AFXKCBFBGDUFAM-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 4
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 4
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 4
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 4
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 239000004793 Polystyrene Substances 0.000 description 4
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 4
- GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical compound NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 229960005305 adenosine Drugs 0.000 description 4
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 239000005289 controlled pore glass Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 4
- 229940104302 cytosine Drugs 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 229960005215 dichloroacetic acid Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 229920002223 polystyrene Polymers 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- 239000001488 sodium phosphate Substances 0.000 description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 description 4
- 239000011877 solvent mixture Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 229940014800 succinic anhydride Drugs 0.000 description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 4
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 4
- 229940045145 uridine Drugs 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
- C07K14/003—Peptide-nucleic acids (PNAs)
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- 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
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- 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
- C12Q1/682—Signal amplification
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- 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
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01J2219/00718—Type of compounds synthesised
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
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- Y02P20/50—Improvements relating to the production of bulk chemicals
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Applications Claiming Priority (1)
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| US71239685A | 1985-03-15 | 1985-03-15 |
Publications (2)
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| DE3650699D1 DE3650699D1 (de) | 1998-10-22 |
| DE3650699T2 true DE3650699T2 (de) | 1999-04-15 |
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| DE8686902189T Expired - Lifetime DE3687030T2 (de) | 1985-03-15 | 1986-03-14 | Stereoregulare polynukleotiden bindende polymere. |
| DE3650349T Expired - Lifetime DE3650349T2 (de) | 1985-03-15 | 1986-03-14 | Immunotestmittel für polynukleotid und verfahren. |
| DE3650699T Expired - Lifetime DE3650699T2 (de) | 1985-03-15 | 1986-03-14 | Immunotestmittel für Polynukleotid und Verfahren |
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| Application Number | Title | Priority Date | Filing Date |
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| DE8686902189T Expired - Lifetime DE3687030T2 (de) | 1985-03-15 | 1986-03-14 | Stereoregulare polynukleotiden bindende polymere. |
| DE3650349T Expired - Lifetime DE3650349T2 (de) | 1985-03-15 | 1986-03-14 | Immunotestmittel für polynukleotid und verfahren. |
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| CA (1) | CA1268404A (enExample) |
| DE (3) | DE3687030T2 (enExample) |
| WO (2) | WO1986005518A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US3211732A (en) * | 1965-10-12 | Pyrazolob:x-d]pyrlil/hdines | ||
| US468950A (en) * | 1892-02-16 | Commutator-brush for electric motors and dynamos | ||
| US3225042A (en) * | 1962-07-31 | 1965-12-21 | Lilly Co Eli | Hydroxymorpholines |
| US3797414A (en) * | 1970-10-29 | 1974-03-19 | M Ahrend | Canted vortex open pit incinerator |
| US4123610A (en) * | 1977-03-09 | 1978-10-31 | The United States Government | Nucleic acid crosslinking agent and affinity inactivation of nucleic acids therewith |
| US4430496A (en) * | 1980-01-17 | 1984-02-07 | Varian Associates, Inc. | Strong anion exchange composition and methods |
| AU543007B2 (en) * | 1980-04-15 | 1985-03-28 | Technicon Instruments Corportion | Agglutination immunoassay |
| US4395486A (en) * | 1981-08-19 | 1983-07-26 | Medical College Of Ga. Research Inst., Inc. | Method for the direct analysis of sickle cell anemia |
| US4515781A (en) * | 1983-02-23 | 1985-05-07 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | 2',5'-Riboadenylate-morpholinoadenylate nucleotides |
| CA1254525A (en) * | 1983-04-13 | 1989-05-23 | Christine L. Brakel | Kit for terminally chemically labeling dna |
| GB8311228D0 (en) * | 1983-04-25 | 1983-06-02 | Fujisawa Pharmaceutical Co | Morpholine derivatives |
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-
1986
- 1986-03-14 EP EP86902595A patent/EP0215942B1/en not_active Expired - Lifetime
- 1986-03-14 DE DE8686902189T patent/DE3687030T2/de not_active Expired - Lifetime
- 1986-03-14 AT AT94116630T patent/ATE171185T1/de not_active IP Right Cessation
- 1986-03-14 WO PCT/US1986/000544 patent/WO1986005518A1/en not_active Ceased
- 1986-03-14 CA CA000504320A patent/CA1268404A/en not_active Expired
- 1986-03-14 AT AT86902189T patent/ATE81872T1/de not_active IP Right Cessation
- 1986-03-14 JP JP61501967A patent/JP3022967B2/ja not_active Expired - Lifetime
- 1986-03-14 DE DE3650349T patent/DE3650349T2/de not_active Expired - Lifetime
- 1986-03-14 DE DE3650699T patent/DE3650699T2/de not_active Expired - Lifetime
- 1986-03-14 AT AT86902595T patent/ATE124999T1/de active
- 1986-03-14 EP EP19860902189 patent/EP0216860B1/en not_active Expired - Lifetime
- 1986-03-14 EP EP94116630A patent/EP0639582B1/en not_active Expired - Lifetime
- 1986-03-14 AU AU56981/86A patent/AU5698186A/en not_active Abandoned
- 1986-03-14 AU AU56613/86A patent/AU5661386A/en not_active Abandoned
- 1986-03-14 WO PCT/US1986/000545 patent/WO1986005519A1/en not_active Ceased
- 1986-03-14 JP JP61502179A patent/JP2528107B2/ja not_active Expired - Lifetime
-
1987
- 1987-09-23 US US07/100,033 patent/US5142047A/en not_active Expired - Lifetime
-
1995
- 1995-08-29 JP JP7220944A patent/JP2670434B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| ATE81872T1 (de) | 1992-11-15 |
| AU5698186A (en) | 1986-10-13 |
| WO1986005519A1 (en) | 1986-09-25 |
| EP0215942A4 (en) | 1988-08-23 |
| EP0216860A1 (en) | 1987-04-08 |
| EP0215942A1 (en) | 1987-04-01 |
| JP2528107B2 (ja) | 1996-08-28 |
| DE3687030T2 (de) | 1993-03-11 |
| EP0215942B1 (en) | 1995-07-12 |
| ATE124999T1 (de) | 1995-07-15 |
| JP2670434B2 (ja) | 1997-10-29 |
| DE3650699D1 (de) | 1998-10-22 |
| DE3687030D1 (enExample) | 1992-12-03 |
| EP0216860B1 (en) | 1992-10-28 |
| EP0639582A3 (en) | 1995-09-06 |
| DE3650349D1 (de) | 1995-08-17 |
| CA1268404A (en) | 1990-05-01 |
| ATE171185T1 (de) | 1998-10-15 |
| DE3650349T2 (de) | 1995-12-14 |
| JP3022967B2 (ja) | 2000-03-21 |
| JPH08193998A (ja) | 1996-07-30 |
| AU5661386A (en) | 1986-10-13 |
| EP0216860A4 (en) | 1989-02-22 |
| US5142047A (en) | 1992-08-25 |
| JPS62502357A (ja) | 1987-09-10 |
| JPS62502338A (ja) | 1987-09-10 |
| EP0639582B1 (en) | 1998-09-16 |
| WO1986005518A1 (en) | 1986-09-25 |
| EP0639582A2 (en) | 1995-02-22 |
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