ES2307829T3 - Composiciones, procedimientos y kits relacionados con compuestos luminescentes. - Google Patents
Composiciones, procedimientos y kits relacionados con compuestos luminescentes. Download PDFInfo
- Publication number
- ES2307829T3 ES2307829T3 ES02802815T ES02802815T ES2307829T3 ES 2307829 T3 ES2307829 T3 ES 2307829T3 ES 02802815 T ES02802815 T ES 02802815T ES 02802815 T ES02802815 T ES 02802815T ES 2307829 T3 ES2307829 T3 ES 2307829T3
- Authority
- ES
- Spain
- Prior art keywords
- group
- heteroalkyl
- compound
- luminophore
- alkyl
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 89
- 239000000203 mixture Substances 0.000 title claims description 49
- 238000000034 method Methods 0.000 title claims description 48
- -1 R 14 Chemical compound 0.000 claims abstract description 63
- 125000004404 heteroalkyl group Chemical group 0.000 claims abstract description 40
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 37
- 125000003118 aryl group Chemical group 0.000 claims abstract description 27
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 20
- 150000002148 esters Chemical class 0.000 claims abstract description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 8
- YHIPILPTUVMWQT-UHFFFAOYSA-N Oplophorus luciferin Chemical class C1=CC(O)=CC=C1CC(C(N1C=C(N2)C=3C=CC(O)=CC=3)=O)=NC1=C2CC1=CC=CC=C1 YHIPILPTUVMWQT-UHFFFAOYSA-N 0.000 claims description 106
- 102000004190 Enzymes Human genes 0.000 claims description 64
- 108090000790 Enzymes Proteins 0.000 claims description 64
- 238000004020 luminiscence type Methods 0.000 claims description 64
- 108090000623 proteins and genes Proteins 0.000 claims description 52
- 102000004169 proteins and genes Human genes 0.000 claims description 49
- 108060001084 Luciferase Proteins 0.000 claims description 35
- 239000000243 solution Substances 0.000 claims description 32
- 239000005089 Luciferase Substances 0.000 claims description 30
- 238000010511 deprotection reaction Methods 0.000 claims description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 108010052090 Renilla Luciferases Proteins 0.000 claims description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 15
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- 108090000371 Esterases Proteins 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 238000001514 detection method Methods 0.000 claims description 6
- 125000002587 enol group Chemical group 0.000 claims description 6
- 125000001033 ether group Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 239000013592 cell lysate Substances 0.000 claims 1
- 230000023077 detection of light stimulus Effects 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 57
- 238000006243 chemical reaction Methods 0.000 description 30
- 239000002609 medium Substances 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- 125000006239 protecting group Chemical group 0.000 description 20
- 238000012360 testing method Methods 0.000 description 18
- 230000003993 interaction Effects 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 239000000523 sample Substances 0.000 description 14
- 239000000758 substrate Substances 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000003556 assay Methods 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 12
- KAEGGIFPLJZUOZ-UHFFFAOYSA-N Renilla luciferin Chemical compound C1=CC(O)=CC=C1C(N1)=CN2C(=O)C(CC=3C=CC=CC=3)=NC2=C1CC1=CC=CC=C1 KAEGGIFPLJZUOZ-UHFFFAOYSA-N 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 150000002085 enols Chemical class 0.000 description 9
- 239000012091 fetal bovine serum Substances 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 239000006188 syrup Substances 0.000 description 8
- 235000020357 syrup Nutrition 0.000 description 8
- 239000012491 analyte Substances 0.000 description 7
- 238000011065 in-situ storage Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 241000254173 Coleoptera Species 0.000 description 5
- FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 5
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
- XOFKYIUILQCCQE-UHFFFAOYSA-N (3-oxo-1-phenylprop-1-en-2-yl) acetate Chemical compound C(C)(=O)OC(C=O)=CC1=CC=CC=C1 XOFKYIUILQCCQE-UHFFFAOYSA-N 0.000 description 4
- HNGMHWCZZWCBON-UHFFFAOYSA-N 3-benzyl-5-phenylpyrazin-2-amine Chemical compound NC1=NC=C(C=2C=CC=CC=2)N=C1CC1=CC=CC=C1 HNGMHWCZZWCBON-UHFFFAOYSA-N 0.000 description 4
- 241001443978 Oplophorus Species 0.000 description 4
- 238000005415 bioluminescence Methods 0.000 description 4
- 230000029918 bioluminescence Effects 0.000 description 4
- 238000000225 bioluminescence resonance energy transfer Methods 0.000 description 4
- NHYXMAKLBXBVEO-UHFFFAOYSA-N bromomethyl acetate Chemical compound CC(=O)OCBr NHYXMAKLBXBVEO-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- BTNMPGBKDVTSJY-UHFFFAOYSA-N keto-phenylpyruvic acid Chemical compound OC(=O)C(=O)CC1=CC=CC=C1 BTNMPGBKDVTSJY-UHFFFAOYSA-N 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- CJIIERPDFZUYPI-UHFFFAOYSA-N oxidized Oplophorus luciferin Chemical compound C1=CC(O)=CC=C1CC(=O)NC1=NC=C(C=2C=CC(O)=CC=2)N=C1CC1=CC=CC=C1 CJIIERPDFZUYPI-UHFFFAOYSA-N 0.000 description 4
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 235000013824 polyphenols Nutrition 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- FBWNMEQMRUMQSO-UHFFFAOYSA-N tergitol NP-9 Chemical compound CCCCCCCCCC1=CC=C(OCCOCCOCCOCCOCCOCCOCCOCCOCCO)C=C1 FBWNMEQMRUMQSO-UHFFFAOYSA-N 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- 239000001903 2-oxo-3-phenylpropanoic acid Substances 0.000 description 2
- BWNPYAKFDUFNND-UHFFFAOYSA-N 4-(5-amino-6-benzylpyrazin-2-yl)phenol Chemical compound NC1=NC=C(C=2C=CC(O)=CC=2)N=C1CC1=CC=CC=C1 BWNPYAKFDUFNND-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- 108010000239 Aequorin Proteins 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 2
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 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 2
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 241000963438 Gaussia <copepod> Species 0.000 description 2
- 102000004366 Glucosidases Human genes 0.000 description 2
- 108010056771 Glucosidases Proteins 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 229910010199 LiAl Inorganic materials 0.000 description 2
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 2
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 241000242739 Renilla Species 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- QGJOFJXBPKBTHA-UHFFFAOYSA-N [O].O=C1N=CC=N1 Chemical compound [O].O=C1N=CC=N1 QGJOFJXBPKBTHA-UHFFFAOYSA-N 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
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- DEDGUGJNLNLJSR-UHFFFAOYSA-N alpha-hydroxycinnamic acid Natural products OC(=O)C(O)=CC1=CC=CC=C1 DEDGUGJNLNLJSR-UHFFFAOYSA-N 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000009795 derivation Methods 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 230000001687 destabilization Effects 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000000695 excitation spectrum Methods 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 150000005235 imidazopyrazines Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 229950010131 puromycin Drugs 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 1
- 150000000182 1,3,5-triazines Chemical class 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
- MSFXPXIVPZXOKN-UHFFFAOYSA-N 2-acetyloxy-3-phenylprop-2-enoic acid Chemical compound CC(=O)OC(C(O)=O)=CC1=CC=CC=C1 MSFXPXIVPZXOKN-UHFFFAOYSA-N 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- XMTQQYYKAHVGBJ-UHFFFAOYSA-N 3-(3,4-DICHLOROPHENYL)-1,1-DIMETHYLUREA Chemical compound CN(C)C(=O)NC1=CC=C(Cl)C(Cl)=C1 XMTQQYYKAHVGBJ-UHFFFAOYSA-N 0.000 description 1
- LIFGYAUYHPQUEA-UHFFFAOYSA-N 5-(oxomethylidene)imidazol-2-one Chemical compound O=C=C1NC(=O)N=C1 LIFGYAUYHPQUEA-UHFFFAOYSA-N 0.000 description 1
- 231100000582 ATP assay Toxicity 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002368 Anger Diseases 0.000 description 1
- 229910014033 C-OH Inorganic materials 0.000 description 1
- WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- 244000182625 Dictamnus albus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108010047357 Luminescent Proteins Proteins 0.000 description 1
- 102000006830 Luminescent Proteins Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108700020962 Peroxidase Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- FWTNBXHOBWPZGV-UHFFFAOYSA-N Renilla luciferyl sulfate Chemical compound C1=CC(O)=CC=C1C(N=C1CC=2C=CC=CC=2)=CN2C1=NC(CC=1C=CC=CC=1)=C2OS(O)(=O)=O FWTNBXHOBWPZGV-UHFFFAOYSA-N 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 241000238584 Vargula Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PQMKYFCFSA-N alpha-D-mannose Chemical compound OC[C@H]1O[C@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-PQMKYFCFSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000003851 biochemical process Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000012625 in-situ measurement Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 238000012886 linear function Methods 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 1
- HOVAGTYPODGVJG-UHFFFAOYSA-N methyl beta-galactoside Natural products COC1OC(CO)C(O)C(O)C1O HOVAGTYPODGVJG-UHFFFAOYSA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 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
- 229930192474 thiophene Natural products 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- 150000008496 α-D-glucosides Chemical class 0.000 description 1
- 150000008498 β-D-glucosides Chemical class 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
- G01N33/533—Production of labelled immunochemicals with fluorescent label
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- C12Q1/66—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving luciferase
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Zoology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- General Physics & Mathematics (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Cell Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Pathology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Luminescent Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Farming Of Fish And Shellfish (AREA)
- Decoration By Transfer Pictures (AREA)
- Electroluminescent Light Sources (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US53482 | 2001-11-02 | ||
| US10/053,482 US7268229B2 (en) | 2001-11-02 | 2001-11-02 | Compounds to co-localize luminophores with luminescent proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2307829T3 true ES2307829T3 (es) | 2008-12-01 |
Family
ID=21984572
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02802815T Expired - Lifetime ES2307829T3 (es) | 2001-11-02 | 2002-11-01 | Composiciones, procedimientos y kits relacionados con compuestos luminescentes. |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US7268229B2 (https=) |
| EP (2) | EP1894933B1 (https=) |
| JP (1) | JP4958388B2 (https=) |
| CN (2) | CN101440089A (https=) |
| AT (1) | ATE399784T1 (https=) |
| CA (1) | CA2462506C (https=) |
| DE (1) | DE60227408D1 (https=) |
| DK (1) | DK1451155T3 (https=) |
| ES (1) | ES2307829T3 (https=) |
| WO (1) | WO2003040100A1 (https=) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1546162B1 (en) | 2002-09-20 | 2011-06-22 | Promega Corporation | Luminescence-based methods and probes for measuring cytochrome p450 activity |
| JP4485470B2 (ja) | 2002-12-23 | 2010-06-23 | プロメガ コーポレイション | ルシフェラーゼ酵素活性を保護するための方法及びキット |
| EP2272972A1 (en) | 2005-05-31 | 2011-01-12 | Promega Corporation | Luminogenic and fluorogenic compounds and methods to detect molecules or conditions |
| US7709468B2 (en) | 2005-09-02 | 2010-05-04 | Abbott Laboratories | Imidazo based heterocycles |
| JP2007081050A (ja) * | 2005-09-13 | 2007-03-29 | Fujifilm Corp | 有機電界発光素子 |
| JP4982737B2 (ja) * | 2006-03-23 | 2012-07-25 | 国立大学法人三重大学 | イミダゾキノキザリノン化学発光物質、その製造法、および発光分析法 |
| JP2007277097A (ja) * | 2006-04-03 | 2007-10-25 | Mie Univ | 発光化合物、発光方法、及びその製造方法 |
| US7709253B2 (en) * | 2006-08-04 | 2010-05-04 | The Board Of Trustees Of The Leland Stanford Junior University | Ligand-regulable transactivation systems, methods of use thereof, methods of detecting estrogen receptor ligands, and methods of differentiating estrogen receptor ligand agonists and antagonists |
| JP5844029B2 (ja) * | 2006-10-24 | 2016-01-13 | ジーン ストリーム ピーティーワイ エルティーディ | ルシフェラーゼシグナルを増強する組成物 |
| US20090075309A1 (en) * | 2007-09-06 | 2009-03-19 | Gambhir Sanjiv S | Bisdeoxycoelenterazine derivatives, methods of use, and BRET2 systems |
| EP2326953B1 (en) | 2008-07-22 | 2018-03-21 | Promega Corporation | Adp detection based luminescent phosphotransferase or atp hydrolase assay |
| US8288559B2 (en) | 2008-08-18 | 2012-10-16 | Promega Corporation | Luminogenic compounds and methods to detect cytochrome P450 3A enzymes |
| WO2010090319A1 (ja) | 2009-02-09 | 2010-08-12 | チッソ株式会社 | セレンテラジン類縁体及びその製造方法 |
| ES2795287T3 (es) | 2009-05-01 | 2020-11-23 | Promega Corp | Luciferasas de Oplophorus sintéticas con mayor emisión de luz |
| JP5605727B2 (ja) * | 2010-04-06 | 2014-10-15 | Ｊｎｃ株式会社 | セレンテラジン類縁体及びセレンテラミド類縁体 |
| SG185481A1 (en) | 2010-05-10 | 2012-12-28 | Univ California | Endoribonuclease compositions and methods of use thereof |
| CN103180324A (zh) * | 2010-11-02 | 2013-06-26 | 普罗美加公司 | 腔肠素衍生物及其使用方法 |
| SG10202103336SA (en) | 2010-11-02 | 2021-04-29 | Promega Corp | Novel coelenterazine substrates and methods of use |
| JP6067019B2 (ja) * | 2011-09-02 | 2017-01-25 | プロメガ コーポレイションＰｒｏｍｅｇａ Ｃｏｒｐｏｒａｔｉｏｎ | 代謝的に活性な細胞の酸化還元状態を評価するための化合物及び方法、ならびにｎａｄ（ｐ）／ｎａｄ（ｐ）ｈを測定するための方法 |
| JP6511720B2 (ja) | 2013-02-28 | 2019-05-15 | Jnc株式会社 | コドン最適化変異エビルシフェラーゼ遺伝子およびその使用方法 |
| JP6040846B2 (ja) | 2013-04-08 | 2016-12-07 | Jnc株式会社 | セレンテラジン類縁体 |
| JP6484987B2 (ja) | 2013-10-21 | 2019-03-20 | Jnc株式会社 | エビルシフェラーゼの触媒蛋白質の変異遺伝子とその使用法 |
| JP6442825B2 (ja) | 2013-12-26 | 2018-12-26 | Jnc株式会社 | エビルシフェラーゼの触媒蛋白質の変異遺伝子とその使用法 |
| US9790537B2 (en) | 2014-01-29 | 2017-10-17 | Promega Corporation | Quinone-masked probes as labeling reagents for cell uptake measurements |
| EP3099691B1 (en) | 2014-01-29 | 2019-11-20 | Promega Corporation | Pro-substrates for live cell applications |
| JP6265020B2 (ja) | 2014-04-16 | 2018-01-24 | Jnc株式会社 | エビルシフェラーゼの触媒蛋白質の変異遺伝子とその使用法 |
| US9732373B2 (en) * | 2014-09-11 | 2017-08-15 | Promega Corporation | Luciferase sequences utilizing infrared-emitting substrates to produce enhanced luminescence |
| JP6814132B2 (ja) | 2014-09-12 | 2021-01-13 | プロメガ コーポレイションＰｒｏｍｅｇａ Ｃｏｒｐｏｒａｔｉｏｎ | 内部タンパク質タグ |
| US9677117B2 (en) | 2014-10-08 | 2017-06-13 | Promega Corporation | Bioluminescent succinate detection assay |
| WO2016210294A1 (en) | 2015-06-25 | 2016-12-29 | Promega Corporation | Thienopyrrole compounds and uses thereof as inhibitors of oplophorus-derived luciferases |
| JP7092677B2 (ja) | 2016-02-15 | 2022-06-28 | プロメガ コーポレイション | セレンテラジン類似体 |
| WO2018049241A1 (en) | 2016-09-09 | 2018-03-15 | Promega Corporation | Dual protected pro-coelenterazine substrates |
| JP7200102B2 (ja) | 2016-11-01 | 2023-01-06 | プロメガ コーポレイション | エネルギー受容体に係留されたセレンテラジン類縁体 |
| EP3548492B1 (en) | 2016-12-01 | 2023-07-05 | Promega Corporation | Cell impermeable coelenterazine analogues |
| WO2018125992A1 (en) | 2016-12-28 | 2018-07-05 | Promega Corporation | Functionalized nanoluc inhibitors |
| EP3395803A1 (en) | 2017-04-28 | 2018-10-31 | Institut Pasteur | Imidazopyrazine derivatives, process for preparation thereof, and their uses as luciferins |
| ES2983923T3 (es) * | 2017-07-06 | 2024-10-28 | Promega Corp | Análogos de la pro-coelenterazina estables en suero |
| JP7419260B2 (ja) | 2018-05-01 | 2024-01-22 | プロメガ コーポレイション | ＮａｎｏＬｕｃ自殺基質としてのセレンテラジン化合物 |
| EP3802514B1 (en) | 2018-06-01 | 2022-08-03 | Promega Corporation | Inhibitors of oplophorus luciferase-derived bioluminescent complexes |
| WO2020023871A1 (en) | 2018-07-27 | 2020-01-30 | Promega Corporation | Quinone-containing conjugates |
| CA3114424A1 (en) | 2018-10-03 | 2020-04-09 | Promega Corporation | Compositions and methods for stabilizing coelenterazine and analogs and derivatives thereof |
| EP4600650A3 (en) | 2019-04-05 | 2025-11-26 | Earli Inc. | Improved methods and compositions for synthetic biomarkers |
| US12582726B1 (en) | 2019-04-05 | 2026-03-24 | Earli Inc. | Synthetic cancer-specific promoters |
| CA3158729A1 (en) | 2019-11-27 | 2021-06-03 | Virginia Kincaid | Multipartite luciferase peptides and polypeptides |
| JP7745550B2 (ja) | 2019-12-10 | 2025-09-29 | プロメガ コーポレイション | 多官能性プローブを使用する生物発光検出用組成物及び生物発光検出方法 |
| US20210363565A1 (en) | 2020-05-22 | 2021-11-25 | Promega Corporation | Enhancement of kinase target engagement |
| US12606863B2 (en) | 2021-05-13 | 2026-04-21 | Promega Corporation | Bioluminescent detection of DNA synthesis |
| CN113683617B (zh) * | 2021-07-16 | 2022-08-30 | 山东大学 | 一种基于腔肠素-h的氘代化合物及其制备方法与应用 |
| WO2023215505A1 (en) | 2022-05-04 | 2023-11-09 | Promega Corporation | Modified dehalogenase with extended surface loop regions |
| EP4519385A2 (en) | 2022-05-04 | 2025-03-12 | Promega Corporation | Bioluminescence-triggered photocatalytic labeling |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4604364A (en) | 1974-01-04 | 1986-08-05 | Kosak Kenneth M | Bioluminescent tracer composition and method of use in immunoassays |
| US4080265A (en) | 1974-08-02 | 1978-03-21 | Antonik Alan S | Method for the determination of creative phosphokinase enzyme |
| US3958938A (en) | 1974-12-16 | 1976-05-25 | Bausch & Lomb Incorporated | Bioluminescent sensor system |
| US4349510A (en) | 1979-07-24 | 1982-09-14 | Seppo Kolehmainen | Method and apparatus for measurement of samples by luminescence |
| SE449004B (sv) | 1981-06-25 | 1987-03-30 | Wallac Oy | Bioluminiscensbestemning av nadh och/eller nadph |
| IT1172385B (it) | 1983-12-21 | 1987-06-18 | Miles Italiana | Composizione e metodo per la determinazione enzimatica di atp ed fmn |
| US4665022A (en) | 1984-02-17 | 1987-05-12 | The Regents Of The University Of California | Bioluminescent assay reagent and method |
| DE3537877A1 (de) | 1985-10-24 | 1987-04-30 | Geiger Reinhard | Luciferin-derivate und immunoassays unter einsatz derartiger luciferin-derivate |
| US5004565A (en) | 1986-07-17 | 1991-04-02 | The Board Of Governors Of Wayne State University | Method and compositions providing enhanced chemiluminescence from 1,2-dioxetanes |
| DE3700908A1 (de) | 1987-01-14 | 1988-07-28 | Geiger Reinhard | Aminoluciferine, verfahren zu deren herstellung und deren verwendung bei der bestimmung von enzymaktivitaeten |
| JPS6447379A (en) | 1987-08-19 | 1989-02-21 | Chisso Corp | Preparation of calcium-dependent oxygenation enzyme |
| JPH04228097A (ja) | 1990-07-02 | 1992-08-18 | Toyo Ink Mfg Co Ltd | ミルク試料からの細胞分離および濃縮方法とそのキット |
| US5283180A (en) | 1990-07-19 | 1994-02-01 | Charm Sciences, Inc. | Bioluminescence method for the determination of pesticides |
| US5374534A (en) | 1990-07-19 | 1994-12-20 | Charm Sciences, Inc. | Method of preparing D-luciferin derivatives |
| US5831102A (en) | 1990-08-30 | 1998-11-03 | Tropix, Inc. | Chemiluminescent 3-(substituted adamant-2'-ylidene) 1,2-dioxetanes |
| US5283179A (en) | 1990-09-10 | 1994-02-01 | Promega Corporation | Luciferase assay method |
| DE69219963T2 (de) | 1991-02-13 | 1997-10-16 | Hamamatsu Photonics K.K., Hamamatsu, Shizuoka | Verfahren zur bestimmung der zahl lebender mikroorganismen |
| US5784162A (en) | 1993-08-18 | 1998-07-21 | Applied Spectral Imaging Ltd. | Spectral bio-imaging methods for biological research, medical diagnostics and therapy |
| JP2856339B2 (ja) | 1991-02-21 | 1999-02-10 | キッコーマン株式会社 | 酵素免疫測定法 |
| JPH08441B2 (ja) | 1992-03-06 | 1996-01-10 | 司 上月 | 容器素材の製造方法 |
| JP3311752B2 (ja) | 1992-07-02 | 2002-08-05 | ソイニ，エルッキ | 生体特異的多変数検定法 |
| US5360728A (en) | 1992-12-01 | 1994-11-01 | Woods Hole Oceanographic Institution (W.H.O.I.) | Modified apoaequorin having increased bioluminescent activity |
| US5648232A (en) | 1993-01-21 | 1997-07-15 | The Secretary Of State For Defence In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland | Microbiological best method and reagents |
| GB9311241D0 (en) | 1993-06-01 | 1993-07-21 | Celsis Ltd | Reagents for use in bioluminescence |
| DE69433967D1 (de) | 1993-10-06 | 2004-09-30 | Univ Florida | Stammzellen-proliferations-faktor |
| JPH07125617A (ja) | 1993-11-02 | 1995-05-16 | Hino Motors Ltd | 坂道発進補助装置 |
| WO1995021191A1 (en) | 1994-02-04 | 1995-08-10 | William Ward | Bioluminescent indicator based upon the expression of a gene for a modified green-fluorescent protein |
| JP3648763B2 (ja) * | 1994-08-23 | 2005-05-18 | 日本油脂株式会社 | ウミホタルルシフェリン誘導体および糖加水分解酵素の定量方法 |
| US5840572A (en) | 1994-10-11 | 1998-11-24 | United States Of America As Represented By The Secretary Of The Navy | Bioluminescent bioassay system |
| JPH08294397A (ja) * | 1995-04-27 | 1996-11-12 | Nippon Oil & Fats Co Ltd | 免疫学的活性物質の測定方法 |
| AU713409B2 (en) | 1995-07-12 | 1999-12-02 | Charm Sciences, Inc. | Test apparatus, system and method for the detection of test samples |
| US6165734A (en) | 1995-12-12 | 2000-12-26 | Applied Spectral Imaging Ltd. | In-situ method of analyzing cells |
| JP3547882B2 (ja) | 1995-12-28 | 2004-07-28 | キッコーマン株式会社 | Ａｔｐ消去剤、ａｔｐ消去法、それを用いた生物細胞測定試薬及び生物細胞測定法 |
| JP3409962B2 (ja) | 1996-03-04 | 2003-05-26 | キッコーマン株式会社 | 生物発光試薬及びその試薬を用いたアデノシンリン酸エステルの定量法並びにその試薬を用いたａｔｐ変換反応系に関与する物質の定量法 |
| US5908751A (en) | 1996-04-26 | 1999-06-01 | Toyo Ink Mfg. Co., Ltd. | Method for detecting and/or determining ATP from microorganism cells in a sample |
| US6416960B1 (en) * | 1996-08-08 | 2002-07-09 | Prolume, Ltd. | Detection and visualization of neoplastic tissues and other tissues |
| US5798263A (en) | 1996-09-05 | 1998-08-25 | Promega Corporation | Apparatus for quantifying dual-luminescent reporter assays |
| GB9626932D0 (en) | 1996-12-24 | 1997-02-12 | Lumitech Limited | Assay methods and kits therefor |
| US6171809B1 (en) | 1998-01-29 | 2001-01-09 | Packard Instrument Company | Method and compositions for detecting luciferase biological samples |
| CA2324648C (en) * | 1998-03-27 | 2013-02-26 | Prolume, Ltd. | Luciferases, fluorescent proteins, nucleic acids encoding the luciferases and fluorescent proteins and the use thereof in diagnostics, high throughput screening and novelty items |
| DE69928255T2 (de) | 1998-06-16 | 2006-11-09 | PerkinElmer BioSignal Inc., Montréal | Biolumineszentes resonanz-energie-transfersystem (bret) und seine anwendung |
| US6214552B1 (en) * | 1998-09-17 | 2001-04-10 | Igen International, Inc. | Assays for measuring nucleic acid damaging activities |
| US20040034225A1 (en) * | 2000-05-17 | 2004-02-19 | Jacqueline Marchand-Brynaert | Aryl-substituted n, n-heterocyclic compounds, method for their preparationand their use in therapeutics and diagnostics |
-
2001
- 2001-11-02 US US10/053,482 patent/US7268229B2/en not_active Expired - Lifetime
-
2002
- 2002-11-01 CA CA2462506A patent/CA2462506C/en not_active Expired - Fee Related
- 2002-11-01 WO PCT/US2002/034972 patent/WO2003040100A1/en not_active Ceased
- 2002-11-01 CN CNA2008101694033A patent/CN101440089A/zh active Pending
- 2002-11-01 AT AT02802815T patent/ATE399784T1/de not_active IP Right Cessation
- 2002-11-01 DK DK02802815T patent/DK1451155T3/da active
- 2002-11-01 ES ES02802815T patent/ES2307829T3/es not_active Expired - Lifetime
- 2002-11-01 CN CNB028266773A patent/CN100439338C/zh not_active Expired - Fee Related
- 2002-11-01 DE DE60227408T patent/DE60227408D1/de not_active Expired - Lifetime
- 2002-11-01 EP EP07025040.2A patent/EP1894933B1/en not_active Expired - Lifetime
- 2002-11-01 JP JP2003542146A patent/JP4958388B2/ja not_active Expired - Lifetime
- 2002-11-01 EP EP02802815A patent/EP1451155B1/en not_active Expired - Lifetime
-
2007
- 2007-08-01 US US11/832,169 patent/US7537912B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JP4958388B2 (ja) | 2012-06-20 |
| CA2462506A1 (en) | 2003-05-15 |
| CN101440089A (zh) | 2009-05-27 |
| EP1451155B1 (en) | 2008-07-02 |
| JP2005515977A (ja) | 2005-06-02 |
| EP1451155A1 (en) | 2004-09-01 |
| DK1451155T3 (da) | 2008-11-10 |
| EP1894933A3 (en) | 2008-03-26 |
| US7537912B2 (en) | 2009-05-26 |
| WO2003040100A1 (en) | 2003-05-15 |
| ATE399784T1 (de) | 2008-07-15 |
| EP1451155A4 (en) | 2006-03-01 |
| CA2462506C (en) | 2010-04-06 |
| DE60227408D1 (de) | 2008-08-14 |
| EP1894933B1 (en) | 2013-07-03 |
| US20080050760A1 (en) | 2008-02-28 |
| US7268229B2 (en) | 2007-09-11 |
| EP1894933A2 (en) | 2008-03-05 |
| CN100439338C (zh) | 2008-12-03 |
| CN1612860A (zh) | 2005-05-04 |
| US20030153090A1 (en) | 2003-08-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2307829T3 (es) | Composiciones, procedimientos y kits relacionados con compuestos luminescentes. | |
| US4774339A (en) | Chemically reactive dipyrrometheneboron difluoride dyes | |
| Takakusa et al. | A novel design method of ratiometric fluorescent probes based on fluorescence resonance energy transfer switching by spectral overlap integral | |
| EP2454261B1 (en) | Imidazo[1,2-alpha]pyrazin-3(7h)-one derivatives bearing a new electron-rich structure | |
| GB2284809A (en) | A fluorescent phenylboronic acid for use in the detection of saccharides | |
| WO2008118445A9 (en) | Methods to quench light from optical reactions | |
| US8178669B2 (en) | Fluorescent probe for peroxynitrite | |
| Resa et al. | New dual fluorescent probe for simultaneous biothiol and phosphate bioimaging | |
| JP2006517413A (ja) | 光を発光反応から消失させる二重酵素アッセイの方法及びキット | |
| Wichmann et al. | Probing phospholipase A2 with fluorescent phospholipid substrates | |
| EP4144738A1 (en) | Coelenterazine analogues tethered to energy acceptors | |
| ES3052851T3 (en) | Coelenterazine analogs for use in luciferase-based assays | |
| Jiang et al. | Novel bioluminescent coelenterazine derivatives with imidazopyrazinone C-6 extended substitution for Renilla luciferase | |
| JP4441606B2 (ja) | スルホン酸エステル化合物およびそれを用いた蛍光プローブ | |
| AU2002363424A1 (en) | Compositions, methods and kits pertaining to luminescent compounds | |
| EP2048140A1 (en) | Deuterated chemiluminescent 1,2-dioxetanes | |
| Zhang et al. | Rigidify styryl-pyridinium dyes to benzo [h] coumarin-based bright two-photon fluorescent probes for cellular bioimaging | |
| JP2014185083A (ja) | セミナフトローダフルオル誘導体および蛍光プローブ | |
| JP6116842B2 (ja) | 標的細胞特異的な光増感用化合物。 | |
| Peterson | Design and synthesis of photoactivated BODIPY dyes for photocaging and superresolution imaging with visible light | |
| Lindberg | Development of coelenterazine derivatives for |