CA2806025C - Luminescent dyes with a water-soluble intramolecular bridge and their biological conjugates - Google Patents
Luminescent dyes with a water-soluble intramolecular bridge and their biological conjugates Download PDFInfo
- Publication number
- CA2806025C CA2806025C CA2806025A CA2806025A CA2806025C CA 2806025 C CA2806025 C CA 2806025C CA 2806025 A CA2806025 A CA 2806025A CA 2806025 A CA2806025 A CA 2806025A CA 2806025 C CA2806025 C CA 2806025C
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- Prior art keywords
- dye
- compound
- conjugate
- biopolymer
- alkyl
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- 239000000975 dye Substances 0.000 title abstract description 214
- -1 acyl azide Chemical class 0.000 claims description 82
- 108090000623 proteins and genes Proteins 0.000 claims description 77
- 102000004169 proteins and genes Human genes 0.000 claims description 77
- 210000004027 cell Anatomy 0.000 claims description 58
- 238000000034 method Methods 0.000 claims description 55
- 238000006243 chemical reaction Methods 0.000 claims description 46
- 125000000217 alkyl group Chemical group 0.000 claims description 41
- 150000001412 amines Chemical class 0.000 claims description 32
- 239000000126 substance Substances 0.000 claims description 31
- 150000003573 thiols Chemical class 0.000 claims description 27
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 26
- 229920001222 biopolymer Polymers 0.000 claims description 25
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 108020004707 nucleic acids Proteins 0.000 claims description 24
- 150000007523 nucleic acids Chemical class 0.000 claims description 24
- 102000039446 nucleic acids Human genes 0.000 claims description 24
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 22
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229920000642 polymer Polymers 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 230000004044 response Effects 0.000 claims description 20
- 150000002148 esters Chemical class 0.000 claims description 19
- 108091034117 Oligonucleotide Proteins 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000005499 phosphonyl group Chemical group 0.000 claims description 12
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 12
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000005382 boronyl group Chemical group 0.000 claims description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 11
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 11
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims description 10
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 238000003556 assay Methods 0.000 claims description 10
- 150000002540 isothiocyanates Chemical class 0.000 claims description 10
- 229920001282 polysaccharide Polymers 0.000 claims description 10
- 230000009870 specific binding Effects 0.000 claims description 10
- 150000003461 sulfonyl halides Chemical class 0.000 claims description 10
- 239000002202 Polyethylene glycol Substances 0.000 claims description 9
- 108010090804 Streptavidin Proteins 0.000 claims description 9
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 9
- 150000004676 glycans Chemical class 0.000 claims description 9
- 239000012528 membrane Substances 0.000 claims description 9
- 230000003287 optical effect Effects 0.000 claims description 9
- 229920001223 polyethylene glycol Polymers 0.000 claims description 9
- 239000005017 polysaccharide Substances 0.000 claims description 9
- 241000894006 Bacteria Species 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 8
- 150000002632 lipids Chemical class 0.000 claims description 8
- 102000004190 Enzymes Human genes 0.000 claims description 7
- 108090000790 Enzymes Proteins 0.000 claims description 7
- 241000700605 Viruses Species 0.000 claims description 7
- 239000002245 particle Substances 0.000 claims description 7
- 150000008064 anhydrides Chemical class 0.000 claims description 6
- 230000000295 complement effect Effects 0.000 claims description 6
- 239000012948 isocyanate Substances 0.000 claims description 6
- 229910052697 platinum Inorganic materials 0.000 claims description 6
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 6
- 108090001008 Avidin Proteins 0.000 claims description 5
- 239000002158 endotoxin Substances 0.000 claims description 5
- 229920006008 lipopolysaccharide Polymers 0.000 claims description 5
- 239000011859 microparticle Substances 0.000 claims description 5
- 108090001090 Lectins Proteins 0.000 claims description 4
- 102000004856 Lectins Human genes 0.000 claims description 4
- 108090001030 Lipoproteins Proteins 0.000 claims description 4
- 102000004895 Lipoproteins Human genes 0.000 claims description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 4
- 150000002513 isocyanates Chemical class 0.000 claims description 4
- 239000002523 lectin Substances 0.000 claims description 4
- 150000001350 alkyl halides Chemical class 0.000 claims description 3
- 210000004102 animal cell Anatomy 0.000 claims description 3
- 150000001540 azides Chemical class 0.000 claims description 3
- 239000002502 liposome Substances 0.000 claims description 3
- 150000003904 phospholipids Chemical class 0.000 claims description 3
- DWAOUXYZOSPAOH-UHFFFAOYSA-N 4-[2-(diethylamino)ethoxy]furo[3,2-g]chromen-7-one;hydrochloride Chemical compound [Cl-].O1C(=O)C=CC2=C1C=C1OC=CC1=C2OCC[NH+](CC)CC DWAOUXYZOSPAOH-UHFFFAOYSA-N 0.000 claims description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 2
- 150000001502 aryl halides Chemical class 0.000 claims description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 2
- 150000002463 imidates Chemical class 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 230000003915 cell function Effects 0.000 claims 3
- 238000012544 monitoring process Methods 0.000 claims 2
- 239000006177 biological buffer Substances 0.000 claims 1
- 230000001747 exhibiting effect Effects 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 230000004936 stimulating effect Effects 0.000 claims 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 claims 1
- 210000005253 yeast cell Anatomy 0.000 claims 1
- 239000000985 reactive dye Substances 0.000 abstract description 23
- 239000007850 fluorescent dye Substances 0.000 abstract description 20
- 230000002209 hydrophobic effect Effects 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 description 103
- 238000002360 preparation method Methods 0.000 description 69
- 239000000243 solution Substances 0.000 description 60
- 239000000523 sample Substances 0.000 description 44
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- 239000000203 mixture Substances 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 29
- 239000007787 solid Substances 0.000 description 28
- 230000015572 biosynthetic process Effects 0.000 description 25
- 238000003786 synthesis reaction Methods 0.000 description 25
- 238000002372 labelling Methods 0.000 description 19
- 125000003729 nucleotide group Chemical group 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000002773 nucleotide Substances 0.000 description 18
- 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 17
- 239000002953 phosphate buffered saline Substances 0.000 description 17
- 239000003153 chemical reaction reagent Substances 0.000 description 16
- 238000002953 preparative HPLC Methods 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 15
- 239000007853 buffer solution Substances 0.000 description 15
- 150000002431 hydrogen Chemical class 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 14
- 239000000298 carbocyanine Substances 0.000 description 14
- 230000021615 conjugation Effects 0.000 description 14
- 239000000758 substrate Substances 0.000 description 14
- 108020004414 DNA Proteins 0.000 description 13
- 150000001298 alcohols Chemical class 0.000 description 13
- 150000001448 anilines Chemical class 0.000 description 13
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 12
- 125000000524 functional group Chemical group 0.000 description 12
- 108060006184 phycobiliprotein Proteins 0.000 description 12
- 239000000306 component Substances 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 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 10
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 10
- 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 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 10
- 229940024606 amino acid Drugs 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 10
- 238000001514 detection method Methods 0.000 description 10
- 150000002989 phenols Chemical class 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 9
- 150000001720 carbohydrates Chemical class 0.000 description 9
- 235000014633 carbohydrates Nutrition 0.000 description 9
- 229940126543 compound 14 Drugs 0.000 description 9
- 238000004132 cross linking Methods 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- QWYZFXLSWMXLDM-UHFFFAOYSA-M pinacyanol iodide Chemical compound [I-].C1=CC2=CC=CC=C2N(CC)C1=CC=CC1=CC=C(C=CC=C2)C2=[N+]1CC QWYZFXLSWMXLDM-UHFFFAOYSA-M 0.000 description 9
- 238000010186 staining Methods 0.000 description 9
- FBVSXKMMQOZUNU-NSHDSACASA-N N2,N6-Bis{[(2-methyl-2-propanyl)oxy]carbonyl}lysine Chemical compound CC(C)(C)OC(=O)NCCCC[C@@H](C(O)=O)NC(=O)OC(C)(C)C FBVSXKMMQOZUNU-NSHDSACASA-N 0.000 description 8
- VHRGRCVQAFMJIZ-UHFFFAOYSA-N cadaverine Chemical compound NCCCCCN VHRGRCVQAFMJIZ-UHFFFAOYSA-N 0.000 description 8
- 150000001735 carboxylic acids Chemical class 0.000 description 8
- 239000013058 crude material Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000006862 quantum yield reaction Methods 0.000 description 8
- 238000012546 transfer Methods 0.000 description 8
- LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 7
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- 235000021317 phosphate Nutrition 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- KPKZJLCSROULON-QKGLWVMZSA-N Phalloidin Chemical compound N1C(=O)[C@@H]([C@@H](O)C)NC(=O)[C@H](C)NC(=O)[C@H](C[C@@](C)(O)CO)NC(=O)[C@H](C2)NC(=O)[C@H](C)NC(=O)[C@@H]3C[C@H](O)CN3C(=O)[C@@H]1CSC1=C2C2=CC=CC=C2N1 KPKZJLCSROULON-QKGLWVMZSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
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- 239000004005 microsphere Substances 0.000 description 6
- 239000002777 nucleoside Substances 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 6
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- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 5
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 5
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
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Classifications
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- 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
- C09B23/08—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing an odd number of >CH- or >C[alkyl]- groups more than three >CH- groups, e.g. polycarbocyanines
- C09B23/083—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing an odd number of >CH- or >C[alkyl]- groups more than three >CH- groups, e.g. polycarbocyanines five >CH- groups
-
- 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
- C09B11/00—Diaryl- or thriarylmethane dyes
- C09B11/04—Diaryl- or thriarylmethane dyes derived from triarylmethanes, i.e. central C-atom is substituted by amino, cyano, alkyl
- C09B11/06—Hydroxy derivatives of triarylmethanes in which at least one OH group is bound to an aryl nucleus and their ethers or esters
- C09B11/08—Phthaleins; Phenolphthaleins; Fluorescein
-
- 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
- C09B11/00—Diaryl- or thriarylmethane dyes
- C09B11/04—Diaryl- or thriarylmethane dyes derived from triarylmethanes, i.e. central C-atom is substituted by amino, cyano, alkyl
- C09B11/10—Amino derivatives of triarylmethanes
- C09B11/24—Phthaleins containing amino groups ; Phthalanes; Fluoranes; Phthalides; Rhodamine dyes; Phthaleins having heterocyclic aryl rings; Lactone or lactame forms of triarylmethane dyes
-
- 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
- C09B11/00—Diaryl- or thriarylmethane dyes
- C09B11/04—Diaryl- or thriarylmethane dyes derived from triarylmethanes, i.e. central C-atom is substituted by amino, cyano, alkyl
- C09B11/26—Triarylmethane dyes in which at least one of the aromatic nuclei is heterocyclic
-
- 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
-
- 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
- C09B57/10—Metal complexes of organic compounds not being dyes in uncomplexed form
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- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
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- Food Science & Technology (AREA)
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- Analytical Chemistry (AREA)
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- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (5)
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| US39999510P | 2010-07-21 | 2010-07-21 | |
| US61/399,995 | 2010-07-21 | ||
| US13/181,107 | 2011-07-12 | ||
| US13/181,107 US8623324B2 (en) | 2010-07-21 | 2011-07-12 | Luminescent dyes with a water-soluble intramolecular bridge and their biological conjugates |
| PCT/US2011/044776 WO2012012595A2 (en) | 2010-07-21 | 2011-07-21 | Luminescent dyes with a water-soluble intramolecular bridge and their biological conjugates |
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| CA2806025A1 CA2806025A1 (en) | 2012-01-26 |
| CA2806025C true CA2806025C (en) | 2017-01-10 |
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| EP (1) | EP2596065B1 (enExample) |
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| ES (1) | ES2667858T3 (enExample) |
| WO (1) | WO2012012595A2 (enExample) |
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| DK2251454T3 (da) | 2009-05-13 | 2014-10-13 | Sio2 Medical Products Inc | Coating og inspektion af beholder |
| US9458536B2 (en) | 2009-07-02 | 2016-10-04 | Sio2 Medical Products, Inc. | PECVD coating methods for capped syringes, cartridges and other articles |
| US11624115B2 (en) | 2010-05-12 | 2023-04-11 | Sio2 Medical Products, Inc. | Syringe with PECVD lubrication |
| US9878101B2 (en) | 2010-11-12 | 2018-01-30 | Sio2 Medical Products, Inc. | Cyclic olefin polymer vessels and vessel coating methods |
| US9272095B2 (en) | 2011-04-01 | 2016-03-01 | Sio2 Medical Products, Inc. | Vessels, contact surfaces, and coating and inspection apparatus and methods |
| AU2012318242A1 (en) | 2011-11-11 | 2013-05-30 | Sio2 Medical Products, Inc. | Passivation, pH protective or lubricity coating for pharmaceutical package, coating process and apparatus |
| US11116695B2 (en) | 2011-11-11 | 2021-09-14 | Sio2 Medical Products, Inc. | Blood sample collection tube |
| WO2013148498A1 (en) | 2012-03-27 | 2013-10-03 | Ventana Medical Systems, Inc. | Signaling conjugates and methods of use |
| EP2846755A1 (en) | 2012-05-09 | 2015-03-18 | SiO2 Medical Products, Inc. | Saccharide protective coating for pharmaceutical package |
| US20150297800A1 (en) | 2012-07-03 | 2015-10-22 | Sio2 Medical Products, Inc. | SiOx BARRIER FOR PHARMACEUTICAL PACKAGE AND COATING PROCESS |
| PL2888257T3 (pl) | 2012-08-21 | 2018-02-28 | Janssen Pharmaceutica Nv | Hapteny kwetiapiny do zastosowania w testach immunologicznych |
| JP6270845B2 (ja) | 2012-08-21 | 2018-01-31 | ヤンセン ファーマシューティカ エヌ．ベー． | アリピプラゾールに対する抗体及びその使用 |
| CN104736564B (zh) | 2012-08-21 | 2019-02-05 | 詹森药业有限公司 | 喹硫平半抗原的抗体及其用途 |
| ES2701062T3 (es) | 2012-08-21 | 2019-02-20 | Janssen Pharmaceutica Nv | Haptenos de olanzapina |
| CA2882595C (en) | 2012-08-21 | 2019-06-04 | Ortho-Clinical Diagnostics, Inc. | Antibodies to olanzapine haptens and use thereof |
| PL2888263T3 (pl) | 2012-08-21 | 2018-10-31 | Janssen Pharmaceutica Nv | Hapteny rysperydonu i paliperydonu |
| EP2888277A4 (en) | 2012-08-21 | 2016-05-18 | Ortho Clinical Diagnostics Inc | ANTIBODIES AGAINST PALIPERIDONE AND USE THEREOF |
| PT2888593T (pt) | 2012-08-21 | 2018-12-12 | Janssen Pharmaceutica Nv | Anticorpos contra risperidona e utilizações dos mesmos |
| CN110054694B (zh) | 2012-08-21 | 2024-02-20 | 詹森药业有限公司 | 阿立哌唑半抗原的抗体及其用途 |
| PL2888592T3 (pl) | 2012-08-21 | 2018-03-30 | Janssen Pharmaceutica Nv | Przeciwciała względem kwetiapiny i ich zastosowania |
| PT2888284T (pt) | 2012-08-21 | 2022-11-18 | Janssen Pharmaceutica Nv | Anticorpos dirigidos contra haptenos de risperidona e a sua utilização |
| CA2882489A1 (en) | 2012-08-21 | 2014-02-27 | Ortho-Clinical Diagnostics, Inc. | Antibodies to paliperidone haptens and use thereof |
| WO2014031662A2 (en) | 2012-08-21 | 2014-02-27 | Ortho-Clinical Diagnostics, Inc | Antibodies to olanzapine and use thereof |
| PT3321254T (pt) | 2012-08-21 | 2020-10-20 | Janssen Pharmaceutica Nv | Haptenos de aripiprazol e seu uso em imunoensaios |
| PL2888258T3 (pl) | 2012-08-21 | 2019-10-31 | Janssen Pharmaceutica Nv | Hapteny paliperydonu |
| ES2628529T3 (es) | 2012-10-24 | 2017-08-03 | Tintes de cianina-azaindolina sustituidos con hidroxamato, y bioconjugados de los mismos | |
| CA2890066C (en) | 2012-11-01 | 2021-11-09 | Sio2 Medical Products, Inc. | Coating inspection method |
| WO2014078666A1 (en) | 2012-11-16 | 2014-05-22 | Sio2 Medical Products, Inc. | Method and apparatus for detecting rapid barrier coating integrity characteristics |
| EP2925903B1 (en) | 2012-11-30 | 2022-04-13 | Si02 Medical Products, Inc. | Controlling the uniformity of pecvd deposition on medical syringes, cartridges, and the like |
| US9764093B2 (en) | 2012-11-30 | 2017-09-19 | Sio2 Medical Products, Inc. | Controlling the uniformity of PECVD deposition |
| EP2961858B1 (en) | 2013-03-01 | 2022-09-07 | Si02 Medical Products, Inc. | Coated syringe. |
| CN105392916B (zh) | 2013-03-11 | 2019-03-08 | Sio2医药产品公司 | 涂布包装材料 |
| US9937099B2 (en) | 2013-03-11 | 2018-04-10 | Sio2 Medical Products, Inc. | Trilayer coated pharmaceutical packaging with low oxygen transmission rate |
| EP2971227B1 (en) | 2013-03-15 | 2017-11-15 | Si02 Medical Products, Inc. | Coating method. |
| CN103288673B (zh) * | 2013-05-28 | 2015-05-06 | 广东药学院 | 一种铂配体及其配合物 |
| EP3693493A1 (en) | 2014-03-28 | 2020-08-12 | SiO2 Medical Products, Inc. | Antistatic coatings for plastic vessels |
| US20150017658A1 (en) * | 2014-05-19 | 2015-01-15 | National Institute Of Standards And Technology | Stain, process for staining and acquiring normalized signal |
| US11077233B2 (en) | 2015-08-18 | 2021-08-03 | Sio2 Medical Products, Inc. | Pharmaceutical and other packaging with low oxygen transmission rate |
| WO2017105928A1 (en) * | 2015-12-16 | 2017-06-22 | Becton, Dickinson And Company | Photostable fluorescent polymeric tandem dyes including luminescent metal complexes |
| WO2017106501A1 (en) | 2015-12-17 | 2017-06-22 | Janssen Pharmaceutica Nv | Antibodies to risperidone and use thereof |
| JP6994461B2 (ja) | 2015-12-17 | 2022-02-04 | ヤンセン ファーマシューティカ エヌ．ベー． | クエチアピンに対する抗体及びその使用 |
| KR102705120B1 (ko) * | 2016-02-26 | 2024-09-09 | 어질런트 테크놀러지스, 인코포레이티드 | 친핵체의 표지화를 개선시키기 위한 비스피리딘의 용도 |
| KR102836360B1 (ko) | 2016-04-15 | 2025-07-23 | 베크만 컬터, 인코포레이티드 | 광활성 거대분자 및 그의 용도 |
| DE102016012162A1 (de) * | 2016-10-11 | 2018-04-12 | Rijksuniversiteit Groningen | Synthese und Struktur chemisch schaltbarer Fluoreszenzsonden auf der Basis von Aminosäuren |
| CN107857788B (zh) * | 2017-07-06 | 2021-04-13 | 江南大学 | 糖基化氟硼二吡咯衍生物、表面糖修饰的纳米胶束及其制备方法和应用 |
| CN108982447B (zh) * | 2018-07-19 | 2020-12-01 | 曲阜师范大学 | 一种用于检测肼的比率式荧光探针的制备方法及应用 |
| US20200048469A1 (en) * | 2018-08-07 | 2020-02-13 | Becton, Dickinson And Company | Polymeric tandem dyes having pendant narrow emission acceptor |
| EP3940000B1 (en) * | 2019-03-14 | 2023-11-22 | Korea University Research and Business Foundation | Carrageenan derivative, probe for labelling macrophages, and method for preparing same |
| CN111454715B (zh) * | 2020-03-30 | 2023-03-21 | 西南大学 | 一种耐水室温磷光材料的制备方法和应用 |
| EP4190795A4 (en) * | 2020-07-30 | 2024-08-28 | FUJIFILM Corporation | Compound, and labeled biological substance in which same is used |
| GB2605404A (en) * | 2021-03-30 | 2022-10-05 | Sumitomo Chemical Co | Sequencing method |
| WO2024129493A1 (en) * | 2022-12-13 | 2024-06-20 | Becton, Dickinson And Company | Sulfonate-containing water-solubilizing peptides |
Family Cites Families (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB870753A (en) | 1957-07-04 | 1961-06-21 | Ilford Ltd | Improvements in or relating to methine dyes |
| US3864644A (en) | 1971-03-22 | 1975-02-04 | Eastman Kodak Co | Dye lasers including rigidized carbocyanine dyes |
| US4011086A (en) | 1975-10-14 | 1977-03-08 | Eastman Kodak Company | Photographic emulsions and elements containing rigidized carbocyanine dyes |
| US4711955A (en) | 1981-04-17 | 1987-12-08 | Yale University | Modified nucleotides and methods of preparing and using same |
| US5171534A (en) | 1984-01-16 | 1992-12-15 | California Institute Of Technology | Automated DNA sequencing technique |
| US5366603A (en) | 1984-03-29 | 1994-11-22 | Li-Cor, Inc. | Sequencing near infrared and infrared fluorescence labeled DNA for detecting useing laser diodes |
| US6086737A (en) | 1984-03-29 | 2000-07-11 | Li-Cor, Inc. | Sequencing near infrared and infrared fluorescence labeled DNA for detecting using laser diodes and suitable labels therefor |
| 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 |
| US5627027A (en) | 1986-04-18 | 1997-05-06 | Carnegie Mellon University | Cyanine dyes as labeling reagents for detection of biological and other materials by luminescence methods |
| US5569587A (en) | 1986-04-18 | 1996-10-29 | Carnegie Mellon University | Method for labeling and detecting materials employing luminescent arysulfonate cyanine dyes |
| US5268486A (en) | 1986-04-18 | 1993-12-07 | Carnegie-Mellon Unversity | Method for labeling and detecting materials employing arylsulfonate cyanine dyes |
| CA1340806C (en) | 1986-07-02 | 1999-11-02 | James Merrill Prober | Method, system and reagents for dna sequencing |
| US5047519A (en) | 1986-07-02 | 1991-09-10 | E. I. Du Pont De Nemours And Company | Alkynylamino-nucleotides |
| US4774339A (en) | 1987-08-10 | 1988-09-27 | Molecular Probes, Inc. | Chemically reactive dipyrrometheneboron difluoride dyes |
| US5049673A (en) | 1987-10-30 | 1991-09-17 | The Regents Of The University Of California | Fluorescent indicator dyes for calcium working at long wavelengths |
| US5162508A (en) | 1987-12-18 | 1992-11-10 | Compagnie Oris Industrie | Rare earth cryptates, processes for their preparation, synthesis intermediates and application as fluorescent tracers |
| US4997928A (en) | 1988-09-15 | 1991-03-05 | E. I. Du Pont De Nemours And Company | Fluorescent reagents for the preparation of 5'-tagged oligonucleotides |
| US4981977A (en) | 1989-06-09 | 1991-01-01 | Carnegie-Mellon University | Intermediate for and fluorescent cyanine dyes containing carboxylic acid groups |
| US5433896A (en) | 1994-05-20 | 1995-07-18 | Molecular Probes, Inc. | Dibenzopyrrometheneboron difluoride dyes |
| US5453517A (en) | 1992-02-25 | 1995-09-26 | Molecular Probes, Inc. | Reactive derivatives of bapta used to make ion-selective chelators |
| US5648270A (en) | 1995-02-06 | 1997-07-15 | Molecular Probes, Inc. | Methods of sensing with fluorescent conjugates of metal-chelating nitrogen heterocycles |
| US5274113A (en) | 1991-11-01 | 1993-12-28 | Molecular Probes, Inc. | Long wavelength chemically reactive dipyrrometheneboron difluoride dyes and conjugates |
| US5405975A (en) | 1993-03-29 | 1995-04-11 | Molecular Probes, Inc. | Fluorescent ion-selective diaryldiaza crown ether conjugates |
| US5567588A (en) | 1990-06-11 | 1996-10-22 | University Research Corporation | Systematic evolution of ligands by exponential enrichment: Solution SELEX |
| 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. |
| 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 |
| US5248782A (en) | 1990-12-18 | 1993-09-28 | Molecular Probes, Inc. | Long wavelength heteroaryl-substituted dipyrrometheneboron difluoride dyes |
| US5187288A (en) | 1991-05-22 | 1993-02-16 | Molecular Probes, Inc. | Ethenyl-substituted dipyrrometheneboron difluoride dyes and their synthesis |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| US5831098A (en) | 1992-03-16 | 1998-11-03 | Minnesota Mining And Manufacturing Company | 2-methyl-4,4a-dihydro-3H-carbazolium salts and dyes derived therefrom |
| WO1994005688A1 (en) | 1992-09-03 | 1994-03-17 | Applied Biosystems, Inc. | 4,7-dichlorofluorescein dyes as molecular probes |
| US5808044A (en) | 1993-01-22 | 1998-09-15 | Pharmacia Biotech Inc. | Indocarbocyanine and benzindocarbocyanine phosphoramidites |
| 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 |
| US5453505A (en) | 1994-06-30 | 1995-09-26 | Biometric Imaging, Inc. | N-heteroaromatic ion and iminium ion substituted cyanine dyes for use as fluorescence labels |
| US6150510A (en) | 1995-11-06 | 2000-11-21 | Aventis Pharma Deutschland Gmbh | Modified oligonucleotides, their preparation and their use |
| DE4445065A1 (de) | 1994-12-07 | 1996-06-13 | Diagnostikforschung Inst | Verfahren zur In-vivo-Diagnostik mittels NIR-Strahlung |
| US6127134A (en) | 1995-04-20 | 2000-10-03 | Carnegie Mellon University | Difference gel electrophoresis using matched multiple dyes |
| US6008373A (en) | 1995-06-07 | 1999-12-28 | Carnegie Mellon University | Fluorescent labeling complexes with large stokes shift formed by coupling together cyanine and other fluorochromes capable of resonance energy transfer |
| US5684142A (en) | 1995-06-07 | 1997-11-04 | Oncor, Inc. | Modified nucleotides for nucleic acid labeling |
| US6004536A (en) | 1995-11-14 | 1999-12-21 | Molecular Probes, Inc. | Lipophilic cyanine dyes with enchanced aqueous solubilty |
| US5668268A (en) | 1995-11-27 | 1997-09-16 | Hybridon, Inc. | Passivated polymer supports for nucleic acid synthesis |
| US5714386A (en) | 1996-01-11 | 1998-02-03 | Board Of Trustees Of The Leland Stanford Junior University | Cy7-allophycocyanin conjugates for use in multiplex fluorescence detection assays |
| US6162931A (en) | 1996-04-12 | 2000-12-19 | Molecular Probes, Inc. | Fluorinated xanthene derivatives |
| WO1997046099A1 (en) * | 1996-06-06 | 1997-12-11 | Neorx Corporation | Liver retention clearing agents |
| US5877310A (en) | 1997-04-25 | 1999-03-02 | Carnegie Mellon University | Glycoconjugated fluorescent labeling reagents |
| US6130101A (en) | 1997-09-23 | 2000-10-10 | Molecular Probes, Inc. | Sulfonated xanthene derivatives |
| US6133445A (en) | 1997-12-17 | 2000-10-17 | Carnegie Mellon University | Rigidized trimethine cyanine dyes |
| US6002003A (en) | 1998-04-14 | 1999-12-14 | Beckman Instruments, Inc. | Cyanine dye activating group with improved coupling selectivity |
| JP2002528723A (ja) | 1998-10-27 | 2002-09-03 | モレキュラー・プロウブズ・インコーポレーテッド | 遷移金属錯体を含有する発光タンパク質染色剤 |
| EP1196398A4 (en) | 1999-07-06 | 2002-11-06 | Surromed Inc | BRIDGED FLUORESCENT DYES, THEIR PRODUCTION AND USE IN DETECTION METHODS |
| US6329205B1 (en) | 1999-08-31 | 2001-12-11 | Molecular Probes, Inc. | Detection method using luminescent europium-based protein stains |
| FR2810406B1 (fr) | 2000-06-15 | 2002-09-20 | Cis Bio Int | Nouveaux cryptates de terre rare peu sensibles a l'extinction de fluorescence |
| WO2002026891A1 (en) | 2000-09-29 | 2002-04-04 | Molecular Probes, Inc. | Modified carbocyanine dyes and their conjugates |
| EP1341557A2 (en) * | 2000-10-27 | 2003-09-10 | Beth Israel Deaconess Medical Center | Non-isotopic detection of osteoblastic activity in vivo using modified bisphosphonates |
| JP2003121956A (ja) * | 2001-10-11 | 2003-04-23 | Fuji Photo Film Co Ltd | ハロゲン化銀写真感光材料 |
| US6800637B2 (en) | 2002-09-12 | 2004-10-05 | Wyeth | Antidepressant indolealkyl derivatives of heterocycle-fused benzodioxan methylamines |
| WO2004101709A1 (en) | 2003-05-09 | 2004-11-25 | Applera Corporation | Phenyl xanthene dyes |
| WO2005000218A2 (en) * | 2003-05-31 | 2005-01-06 | Washington University | Macrocyclic cyanine and indocyanine bioconjugates provide improved biomedical applications |
| DE10329860A1 (de) | 2003-07-02 | 2005-01-20 | Atto-Tec Gmbh | Sulfonamidderivate polycyclischer Farbstoffe für analytische Anwendungen |
| US7344701B2 (en) | 2004-02-03 | 2008-03-18 | Biosearch Technologies, Inc. | Xanthene dyes |
| US7465810B2 (en) * | 2004-10-25 | 2008-12-16 | Anaspec, Inc. | Reactive 1,3′-crosslinked carbocyanine |
| US20070007754A1 (en) | 2005-07-11 | 2007-01-11 | Rybinski Anthony V | Air bag chute |
| WO2007038659A1 (en) * | 2005-09-26 | 2007-04-05 | Invitrogen Corporation | Violet laser excitable dyes and their method of use |
| BRPI0616803B1 (pt) | 2005-10-03 | 2017-04-25 | Ciba Specialty Chemicals Holding Inc | corantes de xanteno, seu processo de preparação, método para tingir as fibras, e composição |
| WO2007114398A1 (ja) * | 2006-03-31 | 2007-10-11 | Wako Pure Chemical Industries, Ltd. | ピラゾール系シアニン色素 |
| US7745645B2 (en) * | 2007-01-22 | 2010-06-29 | Pierce Biotechnology, Inc. | Sulfonamide derivatives of xanthene compounds |
| US7960420B2 (en) | 2007-12-21 | 2011-06-14 | Joyant Pharmaceuticals, Inc | Diazonamide analogs with improved solubility |
-
2011
- 2011-07-12 US US13/181,107 patent/US8623324B2/en active Active
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