JP4943156B2 - シアニン色素標識用試薬 - Google Patents
シアニン色素標識用試薬 Download PDFInfo
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- JP4943156B2 JP4943156B2 JP2006537422A JP2006537422A JP4943156B2 JP 4943156 B2 JP4943156 B2 JP 4943156B2 JP 2006537422 A JP2006537422 A JP 2006537422A JP 2006537422 A JP2006537422 A JP 2006537422A JP 4943156 B2 JP4943156 B2 JP 4943156B2
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- Japan
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- groups
- group
- dye
- sulfobutyl
- methyl
- 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.)
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- 238000002372 labelling Methods 0.000 title claims abstract description 43
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 title abstract 2
- 239000003153 chemical reaction reagent Substances 0.000 title description 3
- 239000000463 material Substances 0.000 claims abstract description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 7
- 125000003118 aryl group Chemical group 0.000 claims abstract description 6
- 125000006850 spacer group Chemical group 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 71
- -1 succinimidyl ester Chemical class 0.000 claims description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 21
- 230000027455 binding Effects 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000000542 sulfonic acid group Chemical group 0.000 claims description 11
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000003729 nucleotide group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000002773 nucleotide Substances 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 4
- UGIZUKGTKCHOEO-UHFFFAOYSA-N (2e)-2-[(2e,4z)-5-[1-(5-carboxypentyl)-3-methyl-5-sulfo-3-(4-sulfobutyl)indol-1-ium-2-yl]penta-2,4-dienylidene]-3-methyl-1,3-bis(4-sulfobutyl)indole-5-sulfonate Chemical compound OC(=O)CCCCCN1C2=CC=C(S(O)(=O)=O)C=C2C(C)(CCCCS(O)(=O)=O)\C1=C/C=C/C=C/C1=[N+](CCCCS(O)(=O)=O)C2=CC=C(S([O-])(=O)=O)C=C2C1(C)CCCCS(O)(=O)=O UGIZUKGTKCHOEO-UHFFFAOYSA-N 0.000 claims description 3
- AXDOQVSFBHMFSE-UHFFFAOYSA-N 1-benzyl-2-[(1e,3e,5e)-5-[1-(5-carboxypentyl)-3-methyl-5-sulfo-3-(4-sulfobutyl)indol-2-ylidene]penta-1,3-dienyl]-3-methyl-3-(4-sulfobutyl)indol-1-ium-5-sulfonate Chemical compound OC(=O)CCCCCN1C2=CC=C(S(O)(=O)=O)C=C2C(C)(CCCCS(O)(=O)=O)\C1=C/C=C/C=C/C(C(C1=CC(=CC=C11)S([O-])(=O)=O)(C)CCCCS(O)(=O)=O)=[N+]1CC1=CC=CC=C1 AXDOQVSFBHMFSE-UHFFFAOYSA-N 0.000 claims description 3
- BLTBKTKORYZZSS-UHFFFAOYSA-N 2-[5-[1-(5-carboxypentyl)-3-methyl-5-sulfo-3-(4-sulfobutyl)indol-1-ium-2-yl]penta-2,4-dienylidene]-1-ethyl-3-methyl-3-(4-sulfobutyl)indole-5-sulfonate Chemical compound OS(=O)(=O)CCCCC1(C)C2=CC(S([O-])(=O)=O)=CC=C2[N+](CC)=C1\C=C\C=C\C=C\1C(CCCCS(O)(=O)=O)(C)C2=CC(S(O)(=O)=O)=CC=C2N/1CCCCCC(O)=O BLTBKTKORYZZSS-UHFFFAOYSA-N 0.000 claims description 3
- QFRWHAVRZLUMIB-UHFFFAOYSA-N 2-[7-[1-(5-carboxypentyl)-3-methyl-5-sulfo-3-(4-sulfobutyl)indol-1-ium-2-yl]hepta-2,4,6-trienylidene]-1-ethyl-3-methyl-3-(4-sulfobutyl)indole-5-sulfonate Chemical compound OS(=O)(=O)CCCCC1(C)C2=CC(S([O-])(=O)=O)=CC=C2[N+](CC)=C1\C=C\C=C\C=C\C=C\1C(CCCCS(O)(=O)=O)(C)C2=CC(S(O)(=O)=O)=CC=C2N/1CCCCCC(O)=O QFRWHAVRZLUMIB-UHFFFAOYSA-N 0.000 claims description 3
- KCLLGUBEMHHCRQ-UHFFFAOYSA-N 2-[7-[5-(carboxymethyl)-3-methyl-1,3-bis(4-sulfobutyl)indol-1-ium-2-yl]hepta-2,4,6-trienylidene]-1-ethyl-3-methyl-3-(4-sulfobutyl)indole-5-sulfonate Chemical compound OS(=O)(=O)CCCCC1(C)C2=CC(S([O-])(=O)=O)=CC=C2[N+](CC)=C1\C=C\C=C\C=C\C=C\1C(CCCCS(O)(=O)=O)(C)C2=CC(CC(O)=O)=CC=C2N/1CCCCS(O)(=O)=O KCLLGUBEMHHCRQ-UHFFFAOYSA-N 0.000 claims description 3
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims description 3
- 125000002619 bicyclic group Chemical group 0.000 claims description 3
- 150000002540 isothiocyanates Chemical class 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 150000008300 phosphoramidites Chemical class 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 210000004027 cell Anatomy 0.000 claims description 2
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- 229940088597 hormone Drugs 0.000 claims description 2
- 230000000813 microbial effect Effects 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 239000003053 toxin Substances 0.000 claims description 2
- 231100000765 toxin Toxicity 0.000 claims description 2
- 108700012359 toxins Proteins 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 150000003460 sulfonic acids Chemical class 0.000 claims 1
- 239000000975 dye Substances 0.000 abstract description 130
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 33
- 102000004169 proteins and genes Human genes 0.000 abstract description 31
- 108090000623 proteins and genes Proteins 0.000 abstract description 30
- 125000005647 linker group Chemical group 0.000 abstract description 7
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 abstract description 6
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical group C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 abstract description 6
- 230000003993 interaction Effects 0.000 abstract description 5
- 108020004707 nucleic acids Proteins 0.000 abstract description 5
- 102000039446 nucleic acids Human genes 0.000 abstract description 5
- 150000007523 nucleic acids Chemical class 0.000 abstract description 5
- 108091034117 Oligonucleotide Proteins 0.000 abstract description 2
- 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 abstract description 2
- 238000010791 quenching Methods 0.000 abstract description 2
- 230000000171 quenching effect Effects 0.000 abstract description 2
- 238000001215 fluorescent labelling Methods 0.000 abstract 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical group OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 53
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- 239000000047 product Substances 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000002299 complementary DNA Substances 0.000 description 23
- 239000000203 mixture Substances 0.000 description 23
- 239000000243 solution Substances 0.000 description 21
- QGKMIGUHVLGJBR-UHFFFAOYSA-M (4z)-1-(3-methylbutyl)-4-[[1-(3-methylbutyl)quinolin-1-ium-4-yl]methylidene]quinoline;iodide Chemical compound [I-].C12=CC=CC=C2N(CCC(C)C)C=CC1=CC1=CC=[N+](CCC(C)C)C2=CC=CC=C12 QGKMIGUHVLGJBR-UHFFFAOYSA-M 0.000 description 19
- 239000003480 eluent Substances 0.000 description 19
- 150000002148 esters Chemical class 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 238000002835 absorbance Methods 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 238000001514 detection method Methods 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- 239000000523 sample Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 229940125782 compound 2 Drugs 0.000 description 12
- 239000000872 buffer Substances 0.000 description 11
- 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 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000007850 fluorescent dye Substances 0.000 description 9
- 125000000524 functional group Chemical group 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 230000002776 aggregation Effects 0.000 description 8
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- 230000008033 biological extinction Effects 0.000 description 7
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 229960002685 biotin Drugs 0.000 description 6
- 235000020958 biotin Nutrition 0.000 description 6
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- 230000005284 excitation Effects 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- GDIYMWAMJKRXRE-UHFFFAOYSA-N (2z)-2-[(2e)-2-[2-chloro-3-[(z)-2-(1,3,3-trimethylindol-1-ium-2-yl)ethenyl]cyclohex-2-en-1-ylidene]ethylidene]-1,3,3-trimethylindole Chemical compound CC1(C)C2=CC=CC=C2N(C)C1=CC=C1C(Cl)=C(C=CC=2C(C3=CC=CC=C3[N+]=2C)(C)C)CCC1 GDIYMWAMJKRXRE-UHFFFAOYSA-N 0.000 description 5
- ZXFJYBCUJLCDIK-UHFFFAOYSA-N 1-(5-carboxypentyl)-2,3-dimethyl-3-(4-sulfobutyl)indol-1-ium-5-sulfonate Chemical compound C1=C(S([O-])(=O)=O)C=C2C(CCCCS(O)(=O)=O)(C)C(C)=[N+](CCCCCC(O)=O)C2=C1 ZXFJYBCUJLCDIK-UHFFFAOYSA-N 0.000 description 5
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- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- JYOHYHWVHZATHI-UHFFFAOYSA-N 1-ethyl-2,3-dimethyl-3-(4-sulfobutyl)indol-1-ium-5-sulfonate Chemical class [O-]S(=O)(=O)C1=CC=C2[N+](CC)=C(C)C(C)(CCCCS(O)(=O)=O)C2=C1 JYOHYHWVHZATHI-UHFFFAOYSA-N 0.000 description 4
- FIZOAOKWJAZVQL-UHFFFAOYSA-N 5-methyl-6-oxoheptane-1-sulfonic acid Chemical compound CC(=O)C(C)CCCCS(O)(=O)=O FIZOAOKWJAZVQL-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 108010090804 Streptavidin Proteins 0.000 description 4
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- TZXLAXDCWLCAHX-UHFFFAOYSA-L disodium 2,3-dimethyl-3-(4-sulfobutyl)indole-5-sulfonate Chemical compound CC1=NC2=C(C1(C)CCCCS(=O)(=O)O)C=C(C=C2)S(=O)(=O)[O-].CC1=NC2=C(C1(C)CCCCS(=O)(=O)O)C=C(C=C2)S(=O)(=O)[O-].[Na+].[Na+] TZXLAXDCWLCAHX-UHFFFAOYSA-L 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
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- MHYFEEDKONKGEB-UHFFFAOYSA-N oxathiane 2,2-dioxide Chemical compound O=S1(=O)CCCCO1 MHYFEEDKONKGEB-UHFFFAOYSA-N 0.000 description 3
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- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical group [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
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- QWYZFXLSWMXLDM-UHFFFAOYSA-M pinacyanol iodide Chemical class [I-].C1=CC2=CC=CC=C2N(CC)C1=CC=CC1=CC=C(C=CC=C2)C2=[N+]1CC QWYZFXLSWMXLDM-UHFFFAOYSA-M 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
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- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
- C09B23/02—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing an odd number of >CH- or >C[alkyl]- groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/08—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Indole Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Thermal Transfer Or Thermal Recording In General (AREA)
- Laminated Bodies (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US51642803P | 2003-10-31 | 2003-10-31 | |
| US60/516,428 | 2003-10-31 | ||
| PCT/GB2004/004573 WO2005044923A1 (en) | 2003-10-31 | 2004-10-29 | Cyanine dye labelling reagents |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007510031A JP2007510031A (ja) | 2007-04-19 |
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Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005017181A2 (en) | 2003-05-20 | 2005-02-24 | Investigen, Inc. | System for detecting polynucleotides |
| ATE522580T1 (de) * | 2003-10-31 | 2011-09-15 | Ge Healthcare Ltd | Cyaninfarbstoffe als markieragenzien |
| EP1781675B1 (en) | 2004-08-13 | 2014-03-26 | Epoch Biosciences, Inc. | Phosphonate fluorescent dyes and conjugates |
| US7767834B2 (en) * | 2004-08-13 | 2010-08-03 | Elitech Holding B.V. | Phosphonylated fluorescent dyes and conjugates |
| DE102006029454A1 (de) * | 2005-12-05 | 2007-06-06 | Dyomics Gmbh | Hydrophile Marker auf Basis von diasteromeren |
| EP1792949B1 (de) | 2005-12-05 | 2010-09-08 | Dyomics GmbH | Hydrophile Marker auf der Basis von diastereomeren Cyaninen |
| EP2010677A4 (en) * | 2006-02-24 | 2010-04-14 | Investigen Inc | METHODS AND COMPOSITIONS FOR DETECTION OF POLYNUCLEOTIDES |
| US7771947B2 (en) | 2007-02-23 | 2010-08-10 | Investigen, Inc. | Methods and compositions for rapid light-activated isolation and detection of analytes |
| WO2008139206A2 (en) * | 2007-05-16 | 2008-11-20 | Ge Healthcare As | Optical imaging agents |
| WO2008139207A2 (en) * | 2007-05-16 | 2008-11-20 | Ge Healthcare As | Labelled hgf binding peptides for imaging |
| US7951959B2 (en) | 2008-09-17 | 2011-05-31 | Thermo Fisher Scientific (Milwaukee) LLC | Hydrophilic labels for biomolecules |
| CN101723874B (zh) * | 2008-10-31 | 2013-09-11 | 深圳迈瑞生物医疗电子股份有限公司 | 花菁类化合物及其在生物样品染色中的用途 |
| WO2010054330A2 (en) * | 2008-11-07 | 2010-05-14 | The General Hospital Corporation | Monofunctional carbocyanine dyes for in vivo and in vitro imaging |
| CN101750476B (zh) * | 2008-12-08 | 2015-06-03 | 深圳迈瑞生物医疗电子股份有限公司 | 血液分析试剂及其使用方法 |
| WO2010120058A2 (ko) * | 2009-04-17 | 2010-10-21 | 한국과학기술연구원 | 생체 분자 표지를 위한 신규 시아닌 화합물 및 그 제조방법 |
| US20100291706A1 (en) * | 2009-05-15 | 2010-11-18 | Millipore Corporation | Dye conjugates and methods of use |
| GB2478359B (en) * | 2010-03-05 | 2018-09-12 | Innova Biosciences Ltd | Conjugation reactions |
| GB201010878D0 (en) * | 2010-06-29 | 2010-08-11 | Ge Healthcare As | Dye compositiion and dye syntheses |
| US20130095040A1 (en) | 2010-06-29 | 2013-04-18 | Ge Healthcare As | Dye compositions and dye syntheses |
| US9012242B2 (en) * | 2010-09-20 | 2015-04-21 | Caliper Life Sciences | Multivalent fluorescent probes |
| EP2625281A2 (en) * | 2010-10-06 | 2013-08-14 | EMD Millipore Corporation | Cyanine compounds, conjugates and method of use |
| EP2655327B1 (en) | 2010-12-21 | 2016-02-24 | Pierce Biotechnology, Inc. | Fluorescent compounds |
| US8877892B2 (en) | 2011-03-15 | 2014-11-04 | Innova Biosciences Limited | Conjugation reactions |
| US8889884B1 (en) | 2011-07-14 | 2014-11-18 | Pierce Biotechnology, Inc. | Phosphine derivatives of fluorescent compounds |
| US9249307B2 (en) | 2011-08-16 | 2016-02-02 | Pierce Biotechnology, Inc. | Benzocyanine compounds |
| EP2758475B1 (en) | 2011-09-23 | 2017-04-26 | Illumina Cambridge Limited | Dyes for labelling molecular ligands |
| US9631096B2 (en) * | 2012-01-20 | 2017-04-25 | Cornell University | Dye compositions, methods of preparation, conjugates thereof, and methods of use |
| CN102608051B (zh) * | 2012-02-21 | 2015-04-08 | 中国科学院化学研究所 | 用于诊断白血病的试剂盒 |
| US9751868B2 (en) | 2012-02-28 | 2017-09-05 | Pierce Biotechnology, Inc. | Benzocyanine compounds |
| WO2013130761A1 (en) | 2012-03-02 | 2013-09-06 | Pierce Biotechnology, Inc. | Indole derivatives as labeling dye for biomolecule |
| CN104540819B (zh) | 2012-08-28 | 2019-04-19 | 皮尔斯生物科技有限公司 | 苯并吡喃鎓化合物 |
| US8809551B1 (en) | 2013-03-08 | 2014-08-19 | Illumina Cambridge Limited | Polymethine compounds and their use as fluorescent labels |
| WO2014165216A1 (en) * | 2013-03-12 | 2014-10-09 | The Trustees Of The University Of Pennsylvania | Diagnosing and treating cancer |
| GB201408077D0 (en) | 2014-05-07 | 2014-06-18 | Illumina Cambridge Ltd | Polymethine compounds and their use as fluorescent labels |
| US20160176819A1 (en) * | 2014-12-19 | 2016-06-23 | Washington University | Asymmetrically charged nir fluorophores |
| GB201508858D0 (en) | 2015-05-22 | 2015-07-01 | Illumina Cambridge Ltd | Polymethine compounds with long stokes shifts and their use as fluorescent labels |
| GB201516987D0 (en) | 2015-09-25 | 2015-11-11 | Illumina Cambridge Ltd | Polymethine compounds and their use as fluorescent labels |
| KR20170101360A (ko) * | 2016-02-26 | 2017-09-06 | 에스에프씨 주식회사 | 시아닌계 화합물, 이를 포함하는 생체분자 표지용 염료, 키트 및 조영제 조성물 |
| KR101953819B1 (ko) * | 2017-12-22 | 2019-03-06 | (주)바이오액츠 | 생체 분자 표지를 위한 신규 시아닌 화합물 및 그 제조방법 |
| CN108752406A (zh) * | 2018-05-29 | 2018-11-06 | 苏州百源基因技术有限公司 | 一种荧光标记的核苷酸及其制备方法和用途 |
| WO2021125295A1 (ja) * | 2019-12-19 | 2021-06-24 | 富士フイルム株式会社 | 化合物及びこれを用いた蛍光標識生体物質 |
| WO2021162133A1 (ko) * | 2020-02-10 | 2021-08-19 | (주)씨바이오멕스 | 생체물질과 연결될 수 있는 양쪽성 형광물질 |
| US11964965B2 (en) | 2020-05-08 | 2024-04-23 | On Target Laboratories, LLC | Methods of manufacture and synthesis of fluorescent dye compounds and uses thereof |
| EP4150009A1 (en) * | 2020-05-12 | 2023-03-22 | Université de Strasbourg | Fluorogenic dimer compound, useful as a probe for detection of endogenous receptors |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5268486A (en) | 1986-04-18 | 1993-12-07 | Carnegie-Mellon Unversity | Method for labeling and detecting materials employing arylsulfonate cyanine dyes |
| US5569587A (en) | 1986-04-18 | 1996-10-29 | Carnegie Mellon University | Method for labeling and detecting materials employing luminescent arysulfonate cyanine dyes |
| US6048982A (en) | 1986-04-18 | 2000-04-11 | Carnegie Mellon University | Cyanine dyes as labeling reagents for detection of biological and other materials by luminescence methods |
| JPH04186342A (ja) * | 1990-11-21 | 1992-07-03 | Fuji Photo Film Co Ltd | 写真感光材料を用いるカラープルーフの作成方法 |
| JPH0531330A (ja) * | 1991-07-31 | 1993-02-09 | Riken Corp | 排ガス浄化方法 |
| JPH05313304A (ja) | 1992-05-11 | 1993-11-26 | Fuji Photo Film Co Ltd | ハロゲン化銀写真感光材料 |
| DE4445065A1 (de) * | 1994-12-07 | 1996-06-13 | Diagnostikforschung Inst | Verfahren zur In-vivo-Diagnostik mittels NIR-Strahlung |
| AU2001294859A1 (en) | 2000-09-29 | 2002-04-08 | Molecular Probes, Inc. | Modified carbocyanine dyes and their conjugates |
| US7615646B2 (en) * | 2002-05-10 | 2009-11-10 | Carnegie Mellon University | Chiral indole intermediates and their fluorescent cyanine dyes containing functional groups |
| ATE522580T1 (de) * | 2003-10-31 | 2011-09-15 | Ge Healthcare Ltd | Cyaninfarbstoffe als markieragenzien |
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2004
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| ATE522580T1 (de) | 2011-09-15 |
| ES2372395T3 (es) | 2012-01-19 |
| EP2360211A1 (en) | 2011-08-24 |
| US20070203343A1 (en) | 2007-08-30 |
| JP2007510031A (ja) | 2007-04-19 |
| US7750163B2 (en) | 2010-07-06 |
| US20100267937A1 (en) | 2010-10-21 |
| CN100577742C (zh) | 2010-01-06 |
| WO2005044923A1 (en) | 2005-05-19 |
| EP1678258A1 (en) | 2006-07-12 |
| HK1093520A1 (en) | 2007-03-02 |
| EP1678258B1 (en) | 2011-08-31 |
| CN1875073A (zh) | 2006-12-06 |
| US8148539B2 (en) | 2012-04-03 |
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