JP5697886B2 - 反応性複素環置換7−ヒドロキシクマリンおよびその複合体 - Google Patents
反応性複素環置換7−ヒドロキシクマリンおよびその複合体 Download PDFInfo
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- JP5697886B2 JP5697886B2 JP2010085260A JP2010085260A JP5697886B2 JP 5697886 B2 JP5697886 B2 JP 5697886B2 JP 2010085260 A JP2010085260 A JP 2010085260A JP 2010085260 A JP2010085260 A JP 2010085260A JP 5697886 B2 JP5697886 B2 JP 5697886B2
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- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- DXBULVYHTICWKT-UHFFFAOYSA-N ethyl 6-bromohexanoate Chemical compound CCOC(=O)CCCCCBr DXBULVYHTICWKT-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000004692 haloalkylcarbonyl group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000005113 hydroxyalkoxy group Chemical group 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229920000592 inorganic polymer Polymers 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 1
- KYLVAMSNNZMHSX-UHFFFAOYSA-N methyl 6-bromohexanoate Chemical compound COC(=O)CCCCCBr KYLVAMSNNZMHSX-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- GWVCIJWBGGVDJJ-UHFFFAOYSA-N n-(4-aminophenyl)sulfonyl-n-(3-methoxypyrazin-2-yl)acetamide Chemical compound COC1=NC=CN=C1N(C(C)=O)S(=O)(=O)C1=CC=C(N)C=C1 GWVCIJWBGGVDJJ-UHFFFAOYSA-N 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229910052755 nonmetal Inorganic materials 0.000 description 1
- 150000002843 nonmetals Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 125000005327 perimidinyl group Chemical group N1C(=NC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000005954 phenoxathiinyl group Chemical group 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 108060006184 phycobiliprotein Proteins 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920006254 polymer film Polymers 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 150000004804 polysaccharides Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229940070891 pyridium Drugs 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000005891 transamination reaction Methods 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- 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
- C09B57/00—Other synthetic dyes of known constitution
- C09B57/02—Coumarine dyes
-
- 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
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/13—Tracers or tags
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Description
HCは複素環であり;
R1、R2、R3、R4、R5、およびR6は独立して、H、ハロゲン、アルキル、アルコキシ、アリールオキシ、チオール、アルキルチオール、アリールチオール、アジド、アミノ、ヒドロキシ、スルホニル、ホスホニル、ボロン酸、L−RG、WSG、または、それ自体がハロゲン、アミノ、ヒドロキシ、スルホニル、ホスホニル、カルボニル、ボロン酸、L−RG、もしくはWSGにより1回もしくは複数回置換されているアルキルもしくはアルコキシであり;
RGは、化学反応性基であり;
Lは、任意選択のリンカーであり;
WSGは、水溶性基であり;
R1、R2、R3、R4、R5、およびR6の少なくとも1つはL−RGを含有し;
R1、R2、R3、R4、R5、およびR6の少なくとも1つはWSGである。
Xは、O、S、NH、またはNR10であり;
Yは、NH、NR11、CH、またはCR12であり;
R1、R2、R3、R4、R5、R6、R10、R11、およびR12は独立して、H、ハロゲン、アルキル、アルコキシ、アリールオキシ、チオール、アルキルチオール、アリールチオール、アジド、アミノ、ヒドロキシ、スルホニル、ホスホニル、ボロン酸、L−RG、WSG、または、それ自体が任意選択で、ハロゲン、アミノ、ヒドロキシ、スルホニル、ホスホニル、カルボニル、ボロン酸、L−RG、もしくはWSGによって1回もしくは複数回置換されているアルキルもしくはアルコキシであり;
RGは、化学反応性基であり;
Lは、任意選択のリンカーであり;
WSGは、水溶性基であり;
R1、R2、R3、R4、R5、R6、R10、R11、およびR12の少なくとも1つはL−RGを含有し;
R1、R2、R3、R4、R5、R6、R10、R11、およびR12の少なくとも1つはWSGである。
Xは、OまたはSであり;
R1、R2、R3、R4、R10、R11、およびR12は独立して、H、ハロゲン、アルキル、アルコキシ、アリールオキシ、チオール、アルキルチオール、アリールチオール、アジド、アミノ、ヒドロキシ、スルホニル、ホスホニル、ボロン酸、L−RG、WSG、または、それ自体が任意選択で、ハロゲン、アミノ、ヒドロキシ、スルホニル、ホスホニル、カルボニル、ボロン酸、L−RG、もしくはWSGによって1回もしくは複数回置換されているアルキルもしくはアルコキシであり;
RGは、化学反応性基であり;
Lは、任意選択のリンカーであり;
WSGは、水溶性基であり;
R1、R2、R3、R4、R10、R11、およびR12の少なくとも1つはL−RGを含有し;
R1、R2、R3、R4、R10、R11、およびR12の少なくとも1つはWSGである。
Xは、OまたはSであり;
R1、R2、R3、R4、R10、およびR11は独立して、H、ハロゲン、アルキル、アルコキシ、アリールオキシ、チオール、アルキルチオール、アリールチオール、アジド、アミノ、ヒドロキシ、スルホニル、ホスホニル、ボロン酸、L−RG、WSG、または、それ自体が任意選択で、ハロゲン、アミノ、ヒドロキシ、スルホニル、ホスホニル、カルボニル、ボロン酸、L−RG、もしくはWSGによって1回もしくは複数回置換されているアルキルもしくはアルコキシであり;
RGは、化学反応性基であり;
Lは、任意選択のリンカーであり;
WSGは、水溶性基であり;
R1、R2、R3、R4、R10、およびR11の少なくとも1つは、L−RGを含有し;
R1、R2、R3、R4、R10、およびR11の少なくとも1つは、WSGであり;
R10およびR11の少なくとも1つはスルホネートを含有する。
Xは、OまたはSであり;
R1、R2、R3、R4、R10、およびR11は独立して、水素、クロロ、フルオロ、シアノ、またはスルホネートであり;
RGは、化学反応性基であり;
Lは、任意選択のリンカーであり;
ただしR10およびR11の少なくとも1つはスルホネートである。
R1、R2、R3、R4、R10、およびR11は独立して、水素、クロロ、フルオロ、シアノ、またはスルホネートであり;
RGは、化学反応性基であり;
Lは、存在せず、またはアルキル、アルコキシ、チオアルキル、アミノ酸、スルホアミノ酸、ポリアミン、ポリエチレングリコール、アリール、アリールアルキル、もしくはヘテロアリールである、任意選択のリンカーであり;
R10およびR11の少なくとも1つはスルホネートである。
R3、R4、R10、およびR11は独立して、水素、クロロ、フルオロ、シアノ、またはスルホネートであり;
nは、1〜10の整数であり;
R10およびR11の少なくとも1つはスルホネートである。
R3およびR4は、独立して、水素、クロロ、フルオロ、またはスルホネートであり;
R10およびR11の少なくとも1つはスルホネートである。
HCは複素環であり;
R1、R2、R3、R4、R5、およびR6は独立して、H、ハロゲン、アルキル、アルコキシ、アリールオキシ、チオール、アルキルチオール、アリールチオール、アジド、アミノ、ヒドロキシ、スルホニル、ホスホニル、ボロン酸、WSG、またはそれ自体がハロゲン、アミノ、ヒドロキシ、スルホニル、ホスホニル、カルボニル、ボロン酸、もしくはWSGによって1回もしくは複数回置換されているアルキルもしくはアルコキシであり;
WSGは、水溶性基であり;
nは、1〜35の整数であり;
SUBは基質であり;
R1、R2、R3、R4、R5、およびR6の少なくとも1つは、任意選択のリンカーLを介してSに共有結合されており;
R1、R2、R3、R4、R5、およびR6の少なくとも1つは、WSGである。
Xは、O、S、NH、またはNR10であり;
Yは、NH、NR11、CH、またはCR12であり;
R1、R2、R3、R4、R5、R6、R10、R11、およびR12は独立して、H、ハロゲン、アルキル、アルコキシ、アリールオキシ、チオール、アルキルチオール、アリールチオール、アジド、アミノ、ヒドロキシ、スルホニル、ホスホニル、ボロン酸、WSG、またはそれ自体が任意選択でハロゲン、アミノ、ヒドロキシ、スルホニル、ホスホニル、カルボニル、ボロン酸、もしくはWSGによって1回もしくは複数回置換されているアルキルもしくはアルコキシであり;
WSGは、水溶性基であり;
nは、1〜35の整数であり;
SUBは、基質であり;
R1、R2、R3、R4、R5、R6、R10、R11、およびR12の少なくとも1つは、任意選択のリンカーLを介してSに共有結合されており;
R1、R2、R3、R4、R5、R6、R10、R11、およびR12の少なくとも1つはWSGである。
Xは、OまたはSであり;
R1、R2、R3、R4、R10、R11、およびR12は独立して、H、ハロゲン、アルキル、アルコキシ、アリールオキシ、チオール、アルキルチオール、アリールチオール、アジド、アミノ、ヒドロキシ、スルホニル、ホスホニル、ボロン酸、WSG、またはそれ自体が任意選択でハロゲン、アミノ、ヒドロキシ、スルホニル、ホスホニル、カルボニル、ボロン酸、もしくはWSGによって1回もしくは複数回置換されているアルキルもしくはアルコキシであり;
WSGは、水溶性基であり;
nは、1〜35の整数であり;
SUBは、基質であり;
R1、R2、R3、R4、R10、R11、およびR12の少なくとも1つは、任意選択のリンカーLを介してSに共有結合されており;
R1、R2、R3、R4、R10、R11、およびR12の少なくとも1つはWSGである。
Xは、OまたはSであり;
R1、R2、R3、R4、R10、およびR11は独立して、H、ハロゲン、アルキル、アルコキシ、アリールオキシ、チオール、アルキルチオール、アリールチオール、アジド、アミノ、ヒドロキシ、スルホニル、ホスホニル、ボロン酸、WSG、またはそれ自体が任意選択でハロゲン、アミノ、ヒドロキシ、スルホニル、ホスホニル、カルボニル、ボロン酸、もしくはWSGによって1回もしくは複数回置換されているアルキルもしくはアルコキシであり;
WSGは、水溶性基であり;
nは、1〜35の整数であり;
SUBは、基質であり;
R1、R2、R3、R4、R10、およびR11の少なくとも1つは、任意選択のリンカーLを介してSに共有結合されており;
R1、R2、R3、R4、R10、およびR11の少なくとも1つはWSGであり;
R10およびR11の少なくとも1つはスルホネートを含有する。
Xは、OまたはSであり;
R1、R2、R3、R4、R10、およびR11は独立して、水素、クロロ、フルオロ、シアノ、またはスルホネートであり;
Lは任意選択のリンカーであり;
SUBは基質であり;
R10およびR11の少なくとも1つは、スルホネートである。
本発明の、反応性の水溶性複素環置換7−ヒドロキシルクマリンは、式1〜8のいずれかに示される一般構造を有する。特定の例について表1に示し、実施例で記述する。
本発明の水溶性複素環置換7−ヒドロキシルクマリンは、4−カルボニルレゾルシノールと複素環酢酸との無水酢酸ベースの縮合から、または4−カルボニルレゾルシノールと活性メチレン化合物との塩基触媒縮合から調製される。これらの基本構造は、上記にて定義された対応するクマリン色素置換基が得られるように、合成中または合成後に、任意選択でさらに置換される。均等な結果をもたらすことができる、多くの可能な変形例があることが理解される。本発明の、反応性クマリン色素の典型的な合成を、図1に示す。文献におけるクマリンのその他の知られている合成方法は、当業者に知られているある修正によって、本発明の化学反応性クマリンを調製するのに適合させることができる(例えば、参照によりそのそれぞれが本明細書に組み込まれている、Bentsenらの特許文献12と、非特許文献7、8、9、10、11、および12参照)。
本発明の、反応性の水溶性複素環置換7−ヒドロキシルクマリン色素は、適切な反応性を有する官能基を含有しまたは含有するように変性された広く様々な有機または無機物質(本明細書では、「基質」と呼ぶ。)と反応することができ、その結果、色素と物質との複合が行われる。有用な色素複合体には、とりわけ、基質がアミノ酸、ヌクレオチド、バイオポリマー(例えば、アミノ酸ポリマー、核酸ポリマー、多糖、炭水化物、または脂質)、抗原、ステロイド、ビタミン、薬物、ハプテン、代謝産物、毒素、環境汚染物質、イオン錯体形成部分、もしくはガラス、プラスチック、またはその他の非生物学的ポリマーである複合体が含まれる。いくつかの実施形態では、基質は、細胞、細胞系、細胞断片もしくは成分、または細胞下粒子(例えば、ウイルス粒子、細菌粒子、またはこれらの成分)である。反応性色素は、典型的には、細胞表面で、細胞膜、オルガネラ、または細胞質において、官能基を標識する。
本発明の蛍光色素複合体は、典型的には基質と反応性の水溶性複素環置換7−ヒドロキシクマリン色素との間の反応の生成物として合成される。反応性色素を使用する色素複合体の調製は、十分に文書で証明されており、例えば、参照により本明細書にそれぞれ組み込まれている文献を参照されたい(例えば、非特許文献16、17、および18参照)。複合体は、典型的には、適切な反応性色素と、複合される物質とを、これらが共に可溶性である適切な溶媒中で混合することから得られる。本明細書に記述される反応性の水溶性複素環置換7−ヒドロキシクメリン色素の水溶液は、容易に生成され、ほとんどの生体材料との複合反応を促進させる。光活性化されたこれら反応性色素の場合、複合は、この反応性色素を活性化するために反応混合物を照射することを必要とする。
本発明の一態様では、本発明の反応性色素は、サンプルまたはサンプルの成分を直接染色しまたは標識するのに使用され、したがってサンプルを特定しまたは定量することができるようになる。化学的反応性色素化合物は、広く様々な材料上で対応する官能基に共有結合することになり、上述のように色素複合体を形成する。
本発明の一態様は、上述の本発明の色素のいずれかを使用した、様々なアッセイの実施を促進させるキットの作製である。本発明のキットは、典型的には本発明の着色または蛍光色素を含み、これらはどちらも、色素複合体を調製するのに有用な化学的反応性標識として存在するものであり、または、複合物質が特異的結合対メンバー、もしくはヌクレオシド、ヌクレオチド、オリゴヌクレオチド、核酸ポリマー、ペプチド、もしくはタンパク質である色素複合体として存在するものである。キットは、任意選択でさらに、典型的には水溶液として存在する1種または複数の緩衝剤を含む。本発明のキットは、任意選択でさらに、追加の検出試薬、得られる標識済み物質を精製するための精製媒体、ルミネセンス標準、酵素、酵素阻害剤、有機溶媒、または本発明のアッセイを実施するための取扱い説明書を含む。
選択された色素の合成戦略、選択された蛍光バイオポリマーの合成、それらの特徴付け、および使用方法の例を、以下の実施例に示す。他の修正例および置換例は、当業者には明らかであろう。以下の実施例は、本発明の実施が例示されるように示すものであり、本発明の範囲全体を限定しまたは画定しようとするものではない。
タンパク質−色素複合体は、例えば、参照によりそのそれぞれが本明細書に組み込まれている文献(例えば、非特許文献25、26、27、28参照)に記載されているような、標準的な手段によって調製することができる。例えばタンパク質−色素複合体は、下記のように本発明のスクシニミジルエステルを使用して調製することができる。
IgGモノクローナル抗体の色素複合体を調製するための好ましいプロトコルについて、以下に記述する。化合物7、13、14、19、25、および60の色素複合体を、以下に述べるように多少変更を加えた状態で、本質的に同じプロトコルを使用して調製した。
DOS=[色素]/[抗体]=Amax・εp/(ε色素・(A280−0.55・Amax))、
ただし[色素]は色素濃度であり、[抗体]は抗体濃度であり、Amaxは色素の最大吸収波長で測定された吸光度であり、A280は280nmで測定された吸光度であり、εpは抗体タンパク質のモル吸光係数であり、ε色素は色素のモル吸光係数である。正確なDOSを得るには、複合体が非複合色素を含むべきではないことに留意すべきである。
ヤギIgG抗体(タンパク質に結合した多糖鎖を有する。)5mgを1mLの0.1M酢酸、0.135M NaCl、pH5.5に溶かしたサンプルを、メタ過ヨウ素酸ナトリウム2.1mgを用い、氷上で、糖タンパク質上に所望量のアルデヒド基を得るのに十分であることが実験により決定された時間にわたって処理し、次いで化合物5と反応させる。反応を、30μLのエチレングリコールを添加することによって停止させる。抗体を、pH7.2のPBSに充填されたSephadex G25カラムで精製する。1M重炭酸ナトリウムの10分の1体積を添加して、pHを上昇させ、化合物5を、色素とタンパク質とのモル比50:1で添加する。反応を、室温で、所望の色素/タンパク質の比を得るのに十分であることが実験により決定された時間にわたって撹拌する。シアノ水素化ホウ素ナトリウムを、10mMの最終濃度まで添加し、反応を室温で4時間撹拌する。抗体複合体を、透析によりまた上述のようにSephadex G25カラムで精製する。ゲル中およびブロット上の過ヨウ素酸酸化糖タンパク質も、本質的には参照により本明細書に組み込まれた文献(例えば、非特許文献29参照)に記載されているように、標識することができる。
β−ガラクトシダーゼ、遊離チオール基に富むタンパク質の溶液を、PBS中に調製する(400μL中2.0mg)。次いでタンパク質溶液を、DMFに溶かしたマレイミド誘導体化合物9の10mg/L溶液で処理する。未反応の色素をスピンカラムで除去する。色素による置換度を、実施例42に記載されるように、遊離色素の吸光係数を使用して推測する。タンパク質濃度は、280nmでの吸光度から推測し、その波長での化合物9の吸光度に合わせて補正される。
アミノデキストラン−色素複合体を、例として平均で13アミノ基により誘導体化された70000MWアミノデキストラン(50mg)を使用して、以下に記述されるように調製する。アミノデキストラン(50mg)を、0.1M NaHCO3中に10mg/mLで溶解する。化合物7、13、14、19、25、または60を、約10〜15の色素/デキストラン比が得られるように添加する。6〜12時間後、得られた複合体をSEPHADEX G−50で精製し、水で溶離する。典型的には6〜10モルの色素が70000MWデキストランと複合する。
微小球を、いくつかの周知のプロトコルのいずれかを使用して、本発明の色素で標識することができる。例を以下に示す。
本発明の色素と複合したヌクレオチドは、参照によりそれぞれが本明細書に組み込まれている文献(例えば、非特許文献30、31、および32参照)に記載されているような、周知の公開されている手順に従って、当業者が容易に調製することができる。特定の複合の例を、以下に記述する。
5’−アミン修飾、18塩基M13プライマー配列(約100μg)を、4μlの水に溶解する。ここに、化合物7、13、14、19、25、または60を100μlの0.1Mホウ酸ナトリウム、pH8.5に溶かした溶液250μgを添加する。16時間後、5M NaCl 10μlおよび冷エタノール3体積を添加する。混合物を−20℃に冷却し、遠心分離し、上澄みをデカンテーションし、ペレットをエタノールで濯ぎ、次いでペレットを100μLの水に溶解する。標識オリゴヌクレオチドをHPLCにより精製する。所望のピークを収集し、蒸発させることにより、蛍光オリゴヌクレオチチド−色素複合体が得られる。
本発明の色素化合物に複合した分析物特異的抗体(即ち、標識抗体)は、フローサイトメトリーによる血液細胞(例えば、全血サンプル)の分析に有用である。標識抗体は、細胞タンパク質を標識(染色)するのに使用され、標識細胞は、フローサイトメトリーによって検出する。
色素複合体を、色素とタンパク質との比のある範囲にわたり、化合物7、13、および25に個別の調製物としてそれぞれ複合されたCD4およびCD45に特異的な抗体(それぞれ、BD Biosciences、San Jose、CAからのクローンSK3および2DD1)を使用して調製した。抗体−色素複合体は、本質的に上記実施例42で述べたように調製した。CD4およびCD45抗体の抗体複合体を使用して、本質的に上記実施例49で述べたように、全血サンプル中のリンパ球を分析した。
色素複合体を、色素/タンパク質の比のある範囲にわたり、化合物7に対して個別の調製物としてそれぞれ複合された4種の異なる抗体、CD3、CD4、CD8、およびCD45抗体(それぞれ、BD Biosciences、San Jose、CAからのクローンSK7、SK3、SK1、および2D1)を使用して調製した。抗体−色素複合体を、本質的に上記実施例42で述べたように調製した。CD3、CD4、CD8、およびCD45抗体の色素複合体を使用して、本質的に上記実施例49で述べたように、全血サンプル中のリンパ球を分析した。
染色インデックス=(S−U)/(2×SD_陰性)、
ただし、Sは染色細胞集団から測定されたメジアン蛍光強度(MFI)であり、Uは非染色細胞集団のMFIであり、SD_陰性は非染色細胞集団の蛍光強度の標準偏差である。図6で、蛍光強度は、メジアン蛍光強度(MFI)として報告される。CD45抗体は全てのリンパ球に結合するので、これらの実験ではバックグラウンドを測定するのに使用される非染色リンパ球集団がなく、染色インデックスを計算することができない。
Claims (16)
- 下式を有することを特徴とする、色素複合体。
Xは、OまたはSであり;
R1、R2、R3、R4、R10、R11、およびR12は独立して、H、ハロゲン、アルキル、アルコキシ、アリールオキシ、チオール、アルキルチオール、アリールチオール、アジド、アミノ、ヒドロキシ、ボロン酸、WSG、または置換アルキルもしくは置換アルコキシであり、前記置換アルキルまたは置換アルコキシは、ハロゲン、アミノ、ヒドロキシ、カルボニル、ボロン酸、またはWSGによって1回もしくは複数回置換されており;
WSGは、スルホネート、チオスルホネート、ホスホネート、ボロネート、アンモニウム、ピリジウム、キノリウム、またはアクリジニウムである水溶性基であり;
nは、1〜35の整数であり;
SUBは、バイオポリマーであり;
R10、R11、およびR12の少なくとも1つは、任意選択のリンカーLを介して前記SUBに共有結合されており、Lは、存在せず、またはアルキル、アルコキシ、チオアルキル、アミノ酸、スルホアミノ酸、ポリアミン、ポリエチレングリコール、アリール、もしくはヘテロアリールであり;
R10、R11、およびR12の少なくとも1つはWSGである] - R 12 は、任意選択のリンカーLを介して前記SUBに共有結合されており、Lは、存在せず、またはアルキル、アルコキシ、チオアルキル、アミノ酸、スルホアミノ酸、ポリアミン、ポリエチレングリコール、アリール、もしくはヘテロアリールであり;
R10およびR11の少なくとも1つはスルホネートを含有することを特徴とする、請求項1に記載の色素複合体。 - 下式を有することを特徴とする、請求項1に記載の色素複合体。
R1、R2、R3、R4、R10、およびR11は独立して、水素、クロロ、フルオロ、またはスルホネートであり;
R10およびR11の少なくとも1つはスルホネートである] - SUBは抗体であることを特徴とする、請求項1から3のいずれか1項に記載の色素複合体。
- 少なくとも請求項1から4のいずれか1項に記載の色素複合体を含む、生物学的アッセイで使用するためのキット。
- R3はクロロであることを特徴とする、請求項1に記載の色素複合体。
- 色素複合体の色素は、水溶性であることを特徴とする、請求項1に記載の色素複合体。
- 色素複合体は、生理学的pHで最大の蛍光を示すことを特徴とする、請求項1に記載の色素複合体。
- 色素複合体は、405nmで吸光度の最大値を示すことを特徴とする、請求項1に記載の色素複合体。
- nは、少なくとも3であることを特徴とする、請求項1に記載の色素複合体。
- nは、少なくとも6であることを特徴とする、請求項1に記載の色素複合体。
- 色素複合体は、自己消光を示さないことを特徴とする、請求項10に記載の色素複合体。
- R1、R2、R3、およびR4は独立して、H、クロロ、またはフルオロであることを特徴とする、請求項1から3のいずれか1項に記載の色素複合体。
- R3およびR4は独立して、クロロまたはフルオロであることを特徴とする、請求項13に記載の色素複合体。
- R10がスルホネートであることを特徴とする、請求項3に記載の色素複合体。
- R11がスルホネートであることを特徴とする、請求項3に記載の色素複合体。
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Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9400273B1 (en) | 2009-12-09 | 2016-07-26 | Life Technologies Corporation | 7-hydroxycoumarin-based cell-tracking reagents |
JP6425538B2 (ja) * | 2011-03-30 | 2018-11-21 | スリーエム イノベイティブ プロパティズ カンパニー | 蛍光性化合物又は発蛍光団化合物、並びにこれらの使用法 |
KR102022483B1 (ko) * | 2012-03-29 | 2019-09-18 | 스미또모 가가꾸 가부시키가이샤 | 염료용 화합물 |
EP2912464B1 (en) | 2012-10-24 | 2017-04-26 | Becton Dickinson and Company | Hydroxamate substituted azaindoline-cyanine dyes and bioconjugates of the same |
SI3313845T1 (sl) * | 2015-06-29 | 2021-01-29 | Immunogen, Inc. | Konjugati spremenjenih protiteles cisteina |
ITUA20161706A1 (it) * | 2016-03-15 | 2017-09-15 | Cyanagen S R L | Nuovi coloranti cumarinici e relativi coniugati |
US11208527B2 (en) | 2016-04-15 | 2021-12-28 | Beckman Coulter, Inc. | Photoactive macromolecules and uses thereof |
JP6821490B2 (ja) * | 2017-04-03 | 2021-01-27 | 日本化薬株式会社 | クマリン化合物又はそれらの塩、並びにこれを含んだ顔料組成物 |
GB201716931D0 (en) | 2017-10-16 | 2017-11-29 | Illumina Cambridge Ltd | New fluorescent compounds and their use as biomarkers |
US20220026434A1 (en) * | 2019-01-21 | 2022-01-27 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V | Advanced methods for automated high-performance identification of carbohydrates and carbohydrate mixture composition patterns and systems therefore as well as methods for calibration of multi wavelength fluorescence detection systems therefore, based on new fluorescent dyes |
CN109721592B (zh) * | 2019-03-04 | 2022-09-30 | 河南理工大学 | 一种含香豆素的氨基吡嗪酰腙衍生物的荧光探针及其制备方法和应用 |
EP3747957A1 (en) | 2019-06-07 | 2020-12-09 | Universidade de Évora | Fluorescent vinyl tiophene and bitiophene coumarins dyes and method of synthesis thereof |
CN112679569B (zh) * | 2020-10-22 | 2022-05-27 | 山西大学 | 一种荧光探针及其制备方法和应用 |
AU2022216619A1 (en) | 2021-02-05 | 2023-09-07 | Beckman Coulter, Inc. | Compositions and methods for preventing non-specific interactions between polymer dyes-antibody conjugates |
CN113121513B (zh) * | 2021-04-26 | 2023-05-16 | 安徽大学 | 一种咔唑-香豆素基腙类化合物及其制备方法和用途 |
EP4334395A1 (en) | 2021-05-04 | 2024-03-13 | Beckman Coulter, Inc. | Uv-absorbing polymers, compositions and uses thereof |
Family Cites Families (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3556959A (en) | 1968-03-29 | 1971-01-19 | Frank Passal | Nickel plating |
IT1088554B (it) | 1977-11-17 | 1985-06-10 | F I D I A Spa | Procedimento sellettivo per la preparazione di derivati della 7-indrossi cumarina |
US4235781A (en) | 1979-09-20 | 1980-11-25 | Thomas C. Elder, Inc. | 6 Or 8 Haloallyl substituted 7-hydroxycoumarins |
US4259233A (en) | 1979-10-23 | 1981-03-31 | Miles Laboratories, Inc. | β-Galactosyl-umbelliferone-labeled protein and polypeptide conjugates |
DE3044128A1 (de) | 1980-11-24 | 1982-07-15 | Bayer Ag, 5090 Leverkusen | Cumarine, verfahren zu ihrer herstellung und ihre verwendung |
US4711955A (en) | 1981-04-17 | 1987-12-08 | Yale University | Modified nucleotides and methods of preparing and using same |
SE8505716D0 (sv) | 1985-12-03 | 1985-12-03 | Biocarb Ab | Novel compounds and conjugates thereof |
US5047519A (en) | 1986-07-02 | 1991-09-10 | E. I. Du Pont De Nemours And Company | Alkynylamino-nucleotides |
US5049673A (en) | 1987-10-30 | 1991-09-17 | The Regents Of The University Of California | Fluorescent indicator dyes for calcium working at long wavelengths |
US5405975A (en) | 1993-03-29 | 1995-04-11 | Molecular Probes, Inc. | Fluorescent ion-selective diaryldiaza crown ether conjugates |
US5648270A (en) | 1995-02-06 | 1997-07-15 | Molecular Probes, Inc. | Methods of sensing with fluorescent conjugates of metal-chelating nitrogen heterocycles |
US5453517A (en) | 1992-02-25 | 1995-09-26 | Molecular Probes, Inc. | Reactive derivatives of bapta used to make ion-selective chelators |
US5516629A (en) | 1990-04-16 | 1996-05-14 | Cryopharm Corporation | Photoinactivation of viral and bacterial blood contaminants using halogenated coumarins |
US5714327A (en) | 1990-07-19 | 1998-02-03 | Kreatech Diagnostics | Platinum-containing compounds, methods for their preparation and applications thereof |
NL9001639A (nl) | 1990-07-19 | 1992-02-17 | Amc Amsterdam | Pt-houdende verbinding, werkwijze voor de bereiding ervan, alsmede toepassing van dergelijke verbindingen. |
US5208148A (en) | 1990-12-07 | 1993-05-04 | Molecular Probes, Inc. | Lipophilic fluorescent glycosidase substrates |
YU187991A (sh) | 1990-12-11 | 1994-09-09 | Hoechst Aktiengesellschaft | 3-(2)-amino-ali tiol-modifikovani, s fluorescentnom bojom vezani nukleozidi, nukleotidi i oligonukleotidi, postupak za njihovo dobijanje i njihova upotreba |
US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
US5516911A (en) | 1993-12-30 | 1996-05-14 | The United States Of America As Represented By The Department Of Health And Human Services | Fluorescent intracellular calcium indicators |
US6150510A (en) | 1995-11-06 | 2000-11-21 | Aventis Pharma Deutschland Gmbh | Modified oligonucleotides, their preparation and their use |
US5741657A (en) | 1995-03-20 | 1998-04-21 | The Regents Of The University Of California | Fluorogenic substrates for β-lactamase and methods of use |
US6342379B1 (en) | 1995-06-07 | 2002-01-29 | The Regents Of The University Of California | Detection of transmembrane potentials by optical methods |
US5684142A (en) | 1995-06-07 | 1997-11-04 | Oncor, Inc. | Modified nucleotides for nucleic acid labeling |
US5668268A (en) | 1995-11-27 | 1997-09-16 | Hybridon, Inc. | Passivated polymer supports for nucleic acid synthesis |
US5955604A (en) | 1996-10-15 | 1999-09-21 | The Regents Of The University Of California | Substrates for β-lactamase and uses thereof |
US5696157A (en) * | 1996-11-15 | 1997-12-09 | Molecular Probes, Inc. | Sulfonated derivatives of 7-aminocoumarin |
US5830912A (en) * | 1996-11-15 | 1998-11-03 | Molecular Probes, Inc. | Derivatives of 6,8-difluoro-7-hydroxycoumarin |
US6221612B1 (en) | 1997-08-01 | 2001-04-24 | Aurora Biosciences Corporation | Photon reducing agents for use in fluorescence assays |
US6372895B1 (en) | 2000-07-07 | 2002-04-16 | 3M Innovative Properties Company | Fluorogenic compounds |
US6207404B1 (en) | 1999-09-30 | 2001-03-27 | Gentest Corporation | Coumarin-based CYP3A fluorescent assay reagents |
US7304168B2 (en) | 2003-08-14 | 2007-12-04 | Board Of Regents, University Of Texas System | Photo-caged fluorescent molecules |
US7674924B2 (en) | 2006-05-22 | 2010-03-09 | Third Wave Technologies, Inc. | Compositions, probes, and conjugates and uses thereof |
US20100029017A1 (en) | 2008-07-29 | 2010-02-04 | Becton, Dickinson And Company | Mono-chlorinated hydroxycoumarin conjugates |
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JP2010254993A (ja) | 2010-11-11 |
US8431416B2 (en) | 2013-04-30 |
CN101914093B (zh) | 2015-08-26 |
ES2548380T3 (es) | 2015-10-16 |
CN101914093A (zh) | 2010-12-15 |
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