CN116577494A - 偶联物在制备检测试剂中的用途 - Google Patents
偶联物在制备检测试剂中的用途 Download PDFInfo
- Publication number
- CN116577494A CN116577494A CN202310725902.0A CN202310725902A CN116577494A CN 116577494 A CN116577494 A CN 116577494A CN 202310725902 A CN202310725902 A CN 202310725902A CN 116577494 A CN116577494 A CN 116577494A
- Authority
- CN
- China
- Prior art keywords
- amikacin
- glucose
- phosphate dehydrogenase
- antibody
- mutant
- 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.)
- Pending
Links
- 238000001514 detection method Methods 0.000 title claims abstract description 33
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 102100031126 6-phosphogluconolactonase Human genes 0.000 claims abstract description 26
- 108010029731 6-phosphogluconolactonase Proteins 0.000 claims abstract description 26
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 claims abstract description 26
- 230000035772 mutation Effects 0.000 claims abstract description 9
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 claims description 55
- 229960004821 amikacin Drugs 0.000 claims description 49
- 102000004190 Enzymes Human genes 0.000 claims description 23
- 108090000790 Enzymes Proteins 0.000 claims description 23
- 238000010168 coupling process Methods 0.000 claims description 11
- 230000008878 coupling Effects 0.000 claims description 8
- 238000005859 coupling reaction Methods 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 238000003018 immunoassay Methods 0.000 claims description 7
- 239000004973 liquid crystal related substance Substances 0.000 claims description 4
- 238000011002 quantification Methods 0.000 abstract 1
- 230000035945 sensitivity Effects 0.000 abstract 1
- 239000000872 buffer Substances 0.000 description 18
- 239000000427 antigen Substances 0.000 description 13
- 102000036639 antigens Human genes 0.000 description 13
- 108091007433 antigens Proteins 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 8
- 125000003396 thiol group Chemical group [H]S* 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 102000010705 glucose-6-phosphate dehydrogenase activity proteins Human genes 0.000 description 7
- 108040005050 glucose-6-phosphate dehydrogenase activity proteins Proteins 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- 238000002835 absorbance Methods 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 229940126586 small molecule drug Drugs 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 229940088597 hormone Drugs 0.000 description 4
- 239000005556 hormone Substances 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 239000004816 latex Substances 0.000 description 4
- 229920000126 latex Polymers 0.000 description 4
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 4
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000002335 preservative effect Effects 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 101710088194 Dehydrogenase Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- -1 bromoacetyl Chemical group 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 238000003908 quality control method Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 102200061299 rs1064794096 Human genes 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 229940035722 triiodothyronine Drugs 0.000 description 3
- 238000004879 turbidimetry Methods 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 2
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102400000064 Neuropeptide Y Human genes 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 208000034953 Twin anemia-polycythemia sequence Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004520 agglutination Effects 0.000 description 2
- VFRROHXSMXFLSN-SLPGGIOYSA-N aldehydo-D-glucose 6-phosphate Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O VFRROHXSMXFLSN-SLPGGIOYSA-N 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 229940045189 glucose-6-phosphate Drugs 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 229940034208 thyroxine Drugs 0.000 description 2
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- UIKROCXWUNQSPJ-VIFPVBQESA-N (-)-cotinine Chemical compound C1CC(=O)N(C)[C@@H]1C1=CC=CN=C1 UIKROCXWUNQSPJ-VIFPVBQESA-N 0.000 description 1
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- PUWBXDQHRRUKNY-CKOVTTQDSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal phosphoric acid Chemical compound OP(O)(O)=O.OP(O)(O)=O.OP(O)(O)=O.OP(O)(O)=O.OP(O)(O)=O.OP(O)(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O PUWBXDQHRRUKNY-CKOVTTQDSA-N 0.000 description 1
- JWUBBDSIWDLEOM-XHQRYOPUSA-N (3e)-3-[(2e)-2-[1-(6-hydroxy-6-methylheptan-2-yl)-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexan-1-ol Chemical compound C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2\C1=C\C=C1/CC(O)CCC1=C JWUBBDSIWDLEOM-XHQRYOPUSA-N 0.000 description 1
- FMNQRUKVXAQEAZ-JNRFBPFXSA-N (5z,8s,9r,10e,12s)-9,12-dihydroxy-8-[(1s)-1-hydroxy-3-oxopropyl]heptadeca-5,10-dienoic acid Chemical compound CCCCC[C@H](O)\C=C\[C@@H](O)[C@H]([C@@H](O)CC=O)C\C=C/CCCC(O)=O FMNQRUKVXAQEAZ-JNRFBPFXSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- GMRQFYUYWCNGIN-ZVUFCXRFSA-N 1,25-dihydroxy vitamin D3 Chemical compound C1([C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=CC=C1C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-ZVUFCXRFSA-N 0.000 description 1
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 1
- DBPWSSGDRRHUNT-UHFFFAOYSA-N 17alpha-hydroxy progesterone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C(=O)C)(O)C1(C)CC2 DBPWSSGDRRHUNT-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- SFRDXVJWXWOTEW-UHFFFAOYSA-N 2-(hydroxymethyl)propane-1,3-diol Chemical compound OCC(CO)CO SFRDXVJWXWOTEW-UHFFFAOYSA-N 0.000 description 1
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- RZQXOGQSPBYUKH-UHFFFAOYSA-N 3-[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]azaniumyl]-2-hydroxypropane-1-sulfonate Chemical compound OCC(CO)(CO)NCC(O)CS(O)(=O)=O RZQXOGQSPBYUKH-UHFFFAOYSA-N 0.000 description 1
- KFGOFTHODYBSGM-IJCBKZNRSA-N 6-Keto-prostaglandin F1a Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC(=O)CCCCC(O)=O KFGOFTHODYBSGM-IJCBKZNRSA-N 0.000 description 1
- KFGOFTHODYBSGM-UHFFFAOYSA-N 6-Oxoprostaglandin F1alpha Natural products CCCCCC(O)C=CC1C(O)CC(O)C1CC(=O)CCCCC(O)=O KFGOFTHODYBSGM-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- 108700016232 Arg(2)-Sar(4)- dermorphin (1-4) Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 101100013805 Aspergillus niger gsdA gene Proteins 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108010075254 C-Peptide Proteins 0.000 description 1
- 235000021318 Calcifediol Nutrition 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 101800001982 Cholecystokinin Proteins 0.000 description 1
- 102100025841 Cholecystokinin Human genes 0.000 description 1
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 1
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 1
- 102100021809 Chorionic somatomammotropin hormone 1 Human genes 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- 101800000414 Corticotropin Proteins 0.000 description 1
- UIKROCXWUNQSPJ-UHFFFAOYSA-N Cotinine Natural products C1CC(=O)N(C)C1C1=CC=CN=C1 UIKROCXWUNQSPJ-UHFFFAOYSA-N 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 description 1
- WDJUZGPOPHTGOT-OAXVISGBSA-N Digitoxin Natural products O([C@H]1[C@@H](C)O[C@@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@@](C)([C@H](C6=CC(=O)OC6)CC5)CC4)CC3)CC2)C[C@H]1O)[C@H]1O[C@@H](C)[C@H](O[C@H]2O[C@@H](C)[C@@H](O)[C@@H](O)C2)[C@@H](O)C1 WDJUZGPOPHTGOT-OAXVISGBSA-N 0.000 description 1
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 1
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 1
- 101800002068 Galanin Proteins 0.000 description 1
- 102000019432 Galanin Human genes 0.000 description 1
- 102400000921 Gastrin Human genes 0.000 description 1
- 108010052343 Gastrins Proteins 0.000 description 1
- 108010007979 Glycocholic Acid Proteins 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- DOMWKUIIPQCAJU-LJHIYBGHSA-N Hydroxyprogesterone caproate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)CCCCC)[C@@]1(C)CC2 DOMWKUIIPQCAJU-LJHIYBGHSA-N 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 241001468196 Leuconostoc pseudomesenteroides Species 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 239000007987 MES buffer Substances 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101710151321 Melanostatin Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- RFDAIACWWDREDC-UHFFFAOYSA-N Na salt-Glycocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCC(O)=O)C)C1(C)C(O)C2 RFDAIACWWDREDC-UHFFFAOYSA-N 0.000 description 1
- 206010029315 Neuromuscular blockade Diseases 0.000 description 1
- 101800003845 Neuropeptide Y Proteins 0.000 description 1
- 101800001814 Neurotensin Proteins 0.000 description 1
- 102000050267 Neurotensin Human genes 0.000 description 1
- 102000004067 Osteocalcin Human genes 0.000 description 1
- 108090000573 Osteocalcin Proteins 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- 108010003044 Placental Lactogen Proteins 0.000 description 1
- 239000000381 Placental Lactogen Substances 0.000 description 1
- 239000004353 Polyethylene glycol 8000 Substances 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 1
- 108010048233 Procalcitonin Proteins 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 108010086019 Secretin Proteins 0.000 description 1
- 102100037505 Secretin Human genes 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- XNRNNGPBEPRNAR-UHFFFAOYSA-N Thromboxane B2 Natural products CCCCCC(O)C=CC1OC(O)CC(O)C1CC=CCCCC(O)=O XNRNNGPBEPRNAR-UHFFFAOYSA-N 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 229920004896 Triton X-405 Polymers 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000011481 absorbance measurement Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 229940126574 aminoglycoside antibiotic Drugs 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 229960005260 amiodarone Drugs 0.000 description 1
- IYIKLHRQXLHMJQ-UHFFFAOYSA-N amiodarone Chemical compound CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(I)=C(OCCN(CC)CC)C(I)=C1 IYIKLHRQXLHMJQ-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 description 1
- 229960003473 androstanolone Drugs 0.000 description 1
- 229960005471 androstenedione Drugs 0.000 description 1
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
- 239000007982 barbital buffer Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229940097217 cardiac glycoside Drugs 0.000 description 1
- 239000002368 cardiac glycoside Substances 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- 229940107137 cholecystokinin Drugs 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
- 229960000258 corticotropin Drugs 0.000 description 1
- 229950006073 cotinine Drugs 0.000 description 1
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229960000648 digitoxin Drugs 0.000 description 1
- WDJUZGPOPHTGOT-XUDUSOBPSA-N digitoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)CC5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O WDJUZGPOPHTGOT-XUDUSOBPSA-N 0.000 description 1
- 229960005156 digoxin Drugs 0.000 description 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229960001348 estriol Drugs 0.000 description 1
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 description 1
- 229960003399 estrone Drugs 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 229940028334 follicle stimulating hormone Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- RFDAIACWWDREDC-FRVQLJSFSA-N glycocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 RFDAIACWWDREDC-FRVQLJSFSA-N 0.000 description 1
- 229940099347 glycocholic acid Drugs 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 229950000801 hydroxyprogesterone caproate Drugs 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- GUWHRJQTTVADPB-UHFFFAOYSA-N lithium azide Chemical compound [Li+].[N-]=[N+]=[N-] GUWHRJQTTVADPB-UHFFFAOYSA-N 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- SLZIZIJTGAYEKK-CIJSCKBQSA-N molport-023-220-247 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)[C@@H](C)O)C1=CNC=N1 SLZIZIJTGAYEKK-CIJSCKBQSA-N 0.000 description 1
- 229950006238 nadide Drugs 0.000 description 1
- 230000001452 natriuretic effect Effects 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 1
- 230000002970 ototoxic effect Effects 0.000 description 1
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 235000019446 polyethylene glycol 8000 Nutrition 0.000 description 1
- 229940085678 polyethylene glycol 8000 Drugs 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 229960002847 prasterone Drugs 0.000 description 1
- CWCXERYKLSEGEZ-KDKHKZEGSA-N procalcitonin Chemical compound C([C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(O)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H]1NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H](N)CSSC1)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 CWCXERYKLSEGEZ-KDKHKZEGSA-N 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960002101 secretin Drugs 0.000 description 1
- OWMZNFCDEHGFEP-NFBCVYDUSA-N secretin human Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(N)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)C1=CC=CC=C1 OWMZNFCDEHGFEP-NFBCVYDUSA-N 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229930002534 steroid glycoside Natural products 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
-
- 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
-
- 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Physics & Mathematics (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Peptides Or Proteins (AREA)
Abstract
本申请涉及偶联物在制备检测试剂中的用途。具体而言,本申请的6‑磷酸葡萄糖脱氢酶突变体相较于野生型6‑磷酸葡萄糖脱氢酶包含选自以下的一个突变或其组合:D306C、D375C、G426C。使用本申请的6‑磷酸葡萄糖脱氢酶突变体所制备的检测试剂盒,其特异性强、灵敏度高、操作方便、检测时间短、定量准确,适合高通量检测。
Description
本申请是2020年1月8日提交的中国专利申请《6-磷酸葡萄糖脱氢酶突变体及其在制备阿米卡星检测试剂中的用途》(申请号2020100173769)的分案申请。
技术领域
本申请涉及生物检测领域,特别是涉及一种突变的酶6-磷酸葡萄糖脱氢酶(简称G6PDH)及其在阿米卡星检测试剂盒中的应用。
背景技术
半抗原,某些小分子物质(分子量小于4000Da),其单独不能诱导免疫应答,即不具备免疫原性,但当其与大分子蛋白质或非抗原性的多聚赖氨酸等载体交联或结合后可获得免疫原性,诱导免疫应答。这些小分子物质可与应答效应产物结合,具备抗原性,它只有免疫反应性,不具免疫原性,又称不完全抗原。
半抗原能与对应抗体结合出现抗原-抗体反应,又不能单独激发人或动物体产生抗体的抗原。它只有免疫反应性,不具免疫原性,又称不完全抗原。大多数多糖、类脂、激素、小分子药物都属于半抗原。如果用化学方法把半抗原与某种蛋白分子(载体)结合,会获得新的免疫原性,并能刺激动物产生相应的抗体。半抗原一旦与蛋白结合,就构成该蛋白质的一个抗原簇。一些比一般半抗原分子量小,但有特异结构的化学活性基团物质(如青霉素、磺胺剂等),称为简单半抗原。
小分子抗原或半抗原因缺乏可作夹心法的两个以上的位点,因此不能用双抗体夹心法进行测定,多采用竞争模式。原理是标本中的抗原和一定量的酶标抗原竞争与固相抗体结合。标本中抗原量含量愈多,结合在固相上的酶标抗原愈少,显色愈浅。小分子激素、药物等ELISA测定多用此法。
阿米卡星(Amikacin)结构式如下所示:
阿米卡星是氨基糖甙类抗生素,用于治疗革兰阴性杆菌所致的尿路、下呼吸道、腹腔、软组织、骨和关节、生殖***等部位的感染,以及败血症等。本品能引起不可逆性耳毒效应,肾毒性甚微,为可逆性,神经肌肉阻滞罕见。
因此,应对该药不良反应监测予以重视。而且由于药物代谢个体存在差异,临床使用时应结合血药浓度监测,制定合理的给药方案,尽量避免不良反应发生。
目前已知的阿米卡星检测方法主要有:高效液相色谱法(HPLC)、化学发光免疫、酶联免疫吸附剂测定(ELISA)、均相酶免疫测定法、胶乳凝集比浊法等方法。HPLC法需要复杂的样品前处理,操作复杂周期长且成本昂贵;发光免疫法试剂成本昂贵,不适合常规治疗药物检测,更不利于大范围推广。现有的均相酶免疫测定法、胶乳凝集比浊法常常因制备工艺复杂、批间差大,应用受到一定限制。
现有技术的方法依赖于对小分子药物(阿米卡星)自身所带反应基团进行的激活,之后再与酶进行反应。这样的偶联方法会出现同一葡萄糖六磷酸脱氢酶上链接有多个阿米卡星的情况,且偶联位点难以确保一致性,难以保证小分子药物和酶之间的定向1:1反应,而导致批间差异大。
发明内容
鉴于本领域的需求,本申请提供了一种新型的6-磷酸葡萄糖脱氢酶突变体、及其在制备阿米卡星检测试剂盒中的用途。
根据一些实施方案,提供了一种6-磷酸葡萄糖脱氢酶突变体。区别于已有发表的专利US006090567A(Homogeneous immunoassays using mutant glucose-6-phosphatedehydrogenases)的6磷酸葡萄糖脱氢酶的突变体,本申请的6-磷酸葡萄糖脱氢酶突变体,其包含选自以下的突变:D306C、G426C、D375C。
根据一些实施方案,提供了一种6-磷酸葡萄糖脱氢酶突变体,所述6-磷酸葡萄糖脱氢酶突变体是选自以下的序列所示:SEQ ID No.2、SEQ ID No.3、SEQ ID No.4。
根据一些实施方案,提供了一种多核苷酸,其编码本申请的6-磷酸葡萄糖脱氢酶突变体。
根据一些实施方案,提供了一种表达载体,其包含本申请的多核苷酸。
根据一些实施方案,提供了一种宿主细胞,其包含本申请的表达载体。宿主细胞可以是原核(如细菌)或真核(如酵母)。
根据一些实施方案,提供了一种偶联物,其是本申请的6-磷酸葡萄糖脱氢酶突变体与半抗原按照摩尔比1:n偶联而成。
在一些实施方案中,n是1至50,例如,1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50。
在一些具体的实施方案中,本申请的6-磷酸葡萄糖脱氢酶突变体与半抗原按照摩尔比优选为1:1。
在一些具体的实施方案中,半抗原的分子量为100Da至4000Da,例如:100、150、200、250、300、350、400、410、420、430、440、450、460、470、480、490、500、520、550、570、600、620、650、700、750、800、850、900、950、1000、1100、1200、1300、1400、1500、1600、1700、1800、1900、2000、2100、2200、2300、2400、2500、2600、2700、2800、2900、3000、3100、3200、3300、3400、3500、3600、3700、3800、3900、4000。
根据本申请,技术人员将理解,“半抗原”还包含其衍生物的形式。为了便于和6-磷酸葡萄糖脱氢酶进行偶联,对于那些自身不带有偶联基团(例如,与巯基反应的基团)的半抗原(例如阿米卡星),可以经改造而带有接头,以便和巯基共价结合。因此,在本申请中,半抗原衍生物是指,经改造而带有巯基反应基团的半抗原。
半抗原选自:小分子药物(如抗生素、精神药物)、激素、代谢物、糖、脂质、氨基酸。
半抗原例如但不限于:茶碱、苯妥英、维生素D、25羟维生素D、1,25双羟维生素D、叶酸、强心甙(包括地高辛、洋地黄毒苷)、酶酚酸、雷帕明、环胞菌素A、乙胺碘复酮、甲胺喋呤、他克莫司、血清氨基酸、胆汁酸、甘胆酸、苯丙氨酸、乙醇、尿尼柯丁代谢产物柯替宁、尿***、尿单羟酚衍生物、神经肽酪氨酸、血浆甘丙素、多胺、组织胺、促甲状腺激素、泌乳素、胎盘泌乳素、生长激素、促***、促***、促肾上腺皮质激素、抗利尿激素、降钙素、降钙素原、甲状旁腺激素、甲状腺素、三碘甲状原氨酸、反三碘甲状原氨酸、游离甲状腺素、游离三碘甲状原氨酸、皮质醇、尿17-羟皮质类固醇、尿17-酮类固醇、脱氢表雄酮及硫酸酯、醛固酮、尿香草苦杏仁酸、血浆肾素、血管紧张素、***、睾酮、双氢睾酮、雄烯二酮、17α羟孕酮、雌酮、雌三醇、***、孕酮、人绒毛膜***、胰岛素、胰岛素原、C肽、胃泌素、血浆***素、血浆6-酮***素F1α、前列环素、肾上腺素、儿茶酚胺、去甲肾上腺素、胆囊收缩素、纳素、环磷酸腺苷、环磷酸鸟苷、血管活性肽、生长抑素、促胰液素、P-物质、神经降压素、血栓素A2、血栓素B2、5羟色胺、神经肽Y、骨钙素。
在具体的实施方案中,半抗原是阿米卡星或其衍生物。
在具体的实施方案中,半抗原是阿米卡星衍生物,其带有巯基反应基团,例如来酰亚胺、溴乙酰基、乙烯基砜或氮丙啶。
在具体的实施方案中,半抗原是阿米卡星衍生物,如式I所示:
其中,
在一些实施方案中,m为1至10的整数,优选1至5的整数,例如1、2、3、4、5。
在一些具体的实施方案中,阿米卡星衍生物具有式II所示的结构:
根据一些实施方案,提供了一种试剂,其包含本申请的偶联物。
根据一些实施方案,提供了本申请的6-磷酸葡萄糖脱氢酶突变体在制备阿米卡星检测试剂中的用途。
根据一些实施方案,提供了本申请的偶联物在制备阿米卡星检测试剂中的用途。
在具体的实施方案中,所述的检测试剂选自:酶联免疫法检测试剂、化学发光免疫法检测试剂、均相酶免疫法检测试剂、胶乳增强免疫比浊法检测试剂。
在具体的实施方案中,所述的检测试剂优选是基于竞争法检测的试剂。
根据一些实施方案,提供了本申请的偶联物在制备阿米卡星检测装置中的用途。
在具体的实施方案中,所述的检测装置可以制备成孔板(例如96-孔板)的形式,比如板上包被根据本申请的试剂。
在具体的实施方案中,所述的检测装置可以制备成颗粒(例如胶乳、磁珠)的形式,比如颗粒上包被根据本申请的试剂。
根据一些实施方案,提供了一种阿米卡星检测试剂盒,其包含:
-第一试剂,所述第一试剂包含底物、缓冲液和阿米卡星抗体;所述底物是6-磷酸葡萄糖脱氢酶的底物;
-第二试剂,所述第二试剂包含本申请的偶联物和缓冲液;
-任选地,校准品,所述校准品包含10mM至500mM缓冲液、0μg/ml至50μg/ml阿米卡星(例如0、3、5、10、20、30、35、40、45、50μg/ml或之间的任意值);以及
-任选地,质控品,所述质控品包含10mM至500mM缓冲液、3μg/ml至40μg/ml(例如3、4、5、10、20、30、40μg/ml或之间的任意值)阿米卡星。
根据一个实施方案,提供了一种阿米卡星检测试剂盒,其包含:
第一试剂,其包含:
10mM至500mM缓冲液、
5mM至50mM底物、
0.01μg/ml至10μg/ml阿米卡星抗体(0.1、0.2、0.3、0.4、0.5、0.6、0.7、0.8、0.9、1.0、1.1、1.2、1.5、2、3、4、5μg/ml)、
0.1g/L至5g/L稳定剂、
0.1g/L至5g/L表面活性剂、
0.1g/L至5g/L防腐剂;
第二试剂,其包含:
10mM至500mM缓冲液、
0.01μg/ml至10μg/ml根据本申请的偶联物(0.05、0.06、0.07、0.08、0.09、0.1、0.2、0.3、0.4、0.5、0.6、0.7、0.8、0.9、1.0μg/ml)、
0.1g/L至5g/L稳定剂、
0.1g/L至5g/L表面活性剂、
0.1g/L至5g/L防腐剂。
在一些实施方案中,所述缓冲液选自以下的一种或组合:TAPS、氨基丁三醇缓冲液、磷酸盐缓冲液、Tris-HCl缓冲液、柠檬酸-柠檬酸钠缓冲液、巴比妥缓冲液、甘氨酸缓冲液、硼酸盐缓冲液、三羟甲基甲烷缓冲液;优选,磷酸盐缓冲液;所述缓冲液的浓度为10mmol/L至500mmol/L,优选50至100mM;所述缓冲液的pH为7至8。
在一些实施方案中,所述稳定剂选自以下的一种或组合:牛血清白蛋白、海藻糖、甘油、蔗糖、甘露醇、甘氨酸、精氨酸、聚乙二醇6000、聚乙二醇8000;优选牛血清白蛋白。
在一些实施方案中,所述表面活性剂选自以下的一种或组合:Brij35、Triton X-100、Triton X-405、Tween20、Tween30、Tween80、椰子油脂肪酸二乙醇酰胺、AEO7,优选Tween20。
在一些实施方案中,所述的防腐剂选自以下的一种或组合:叠氮化物、MIT、生物防腐剂PC(如PC-300)、硫柳汞;所述叠氮化物选自:叠氮钠、叠氮锂。
在一些实施方案中,所述底物包含:6-磷酸葡糖糖、β-烟酰胺腺嘌呤二核苷酸。
在一些具体的实施方案中,所述阿米卡星抗体源自:小鼠、大鼠、猫、犬、灵长类、牛、马、羊、骆驼科、禽、人。
在一些具体的实施方案中,所述阿米卡星抗体选自:单抗、多抗、重组抗体、嵌合抗体、抗原结合片段。
根据一些实施方案,提供了一种偶联物的制备方法,包括步骤:
1)提供根据本申请的阿米卡星衍生物,尤其是在非质子性溶剂(例如但不限于乙腈、二甲基甲酰胺、二甲基亚砜)中提供根据本申请的阿米卡星衍生物;
2)提供6-磷酸葡萄糖脱氢酶突变体,优选在缓冲液(其提供反应环境,例如但不限于PBS、Tris、TAPS、TAPSO,所述缓冲液pH为6.0至8.0)中提供6-磷酸葡萄糖脱氢酶突变体;
3)在18℃至28℃,将所述6-磷酸葡萄糖脱氢酶突变体和所述阿米卡星衍生物,按照阿米卡星衍生物:酶=500:1至1:500摩尔比(优选50:1至1:50)接触1小时至4小时(1、1.5、2、2.5、3、3.5、4小时、或之间的任何值,优选2小时至3小时)使得所述阿米卡星衍生物和所述6-磷酸葡萄糖脱氢酶突变体发生偶联,得到所述种偶联物;
4)根据需要,任选对所述种偶联物进行纯化,例如脱盐处理等。
在一些实施方案中,反应体系中半抗原和酶的接触摩尔比1:n,其中n是1至500,例如,1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、100、200、300、400、500及其任意上述数值之间的范围;优选50。
在一些实施方案中,反应体系中半抗原和酶的接触摩尔比n:1,其中n是1至500,例如,1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、100、200、300、400、500及其任意上述数值之间的范围;优选50。在一些具体的实施方案中,步骤1)和2)可互换或并行。
在一些具体的实施方案中,在偶联之前,所述6-磷酸葡萄糖脱氢酶包含一个或多个游离的巯基,从而允许和阿米卡星实现定向反应。
野生型6-磷酸葡萄糖脱氢酶不含游离的巯基,因此在一些具体的实施方案中,6-磷酸葡萄糖脱氢酶是经过基因工程改造的,使其在特定位点(306、375或426位)上的氨基酸突变为半胱氨酸,从而带有一个游离巯基。
附图说明
图1.G6PDH(野生型)氨基酸序列(SEQ ID No.1);源自明串珠菌属假肠膜明串珠菌Leuconostoc pseudomesenteroides。
图2.G6PDH(D306C)氨基酸序列(SEQ ID No.2)。
图3.G6PDH(D375C)氨基酸序列(SEQ ID No.3)。
图4.G6PDH(G426C)氨基酸序列(SEQ ID No.4)。
具体实施方式
实施例
实施例1.阿米卡星衍生物的合成
按照上述流程,将阿米卡星(123mg,0.21mmol)和化合物1(64mg,0.21mmol)溶于水5mL中,室温(18-28℃)搅拌5h。HPLC分离得到阿米卡星衍生物(100mg,61%)。
经质谱和核磁鉴定,阿米卡星衍生物结构正确无误。本实施例使得阿米卡星带有一个可以和酶结合的基团。
实施例2.阿米卡星衍生物与G6PDH分子的偶联
一、本申请的偶联方法
根据本申请的G6PDH-阿米卡星偶联物,按照以下方式进行偶联:阿米卡星衍生物分子上的巯基反应性基团(如但不限于马来酰亚胺基团)与G6PDH分子上的巯基共价结合。
1.将实施例1制备的阿米卡星衍生物溶于N,N-二甲基甲酰胺中(10mg/ml);
2.G6PDH溶液:G6PDH突变体溶于PB 100mmol、NaCl 100mmol,pH 8.0,6mg/ml;
3.将200μl G6PDH溶液加入至750μl缓冲溶液(0.05M Na2HPO4、150mM NaCl、10mMEDTA、0.1% NaN3、pH=7.2)中;然后向其中加入阿米卡星衍生物的N,N-二甲基甲酰胺溶液50μl;
4.上述混合溶液,在室温(18-28℃)下充分震荡2-3小时,脱盐处理,收集蛋白峰,所得产物即G6PDH-阿米卡星偶联物。
二、对照偶联方法
准确称取100至300mg阿米卡星,并用5至15mL无水乙醇溶解;
在上述溶液中滴加10至200mM的高碘酸钠5至15mL,并轻微振荡,室温搅拌反应0.5-2小时;
滴加0.5至2M的乙二醇0.5至1mL,室温搅拌反应5至10分钟;
将上述反应混合物滴加到5至15mL正在搅拌中的2至3%的G6PDH溶液中,并调节溶液pH到9.0至9.5,继续搅拌反应0.5至2小时,并使溶液pH稳定;
加入100至200mg四氢硼钠,搅拌还原12至24小时;
通过G-25凝胶层析柱纯化得到G6PDH-阿米卡星偶联物。
实施例3.试剂盒的制备
制备以下检测阿米卡星的试剂盒,其包含:
试剂R1,包含:
Tris缓冲液100mM,pH 7.0
10mM 6-磷酸葡萄糖
10mMβ-烟酰胺腺嘌呤二核苷酸
0.5μg/ml阿米卡星抗体(市售抗体,无特殊限制)
1g/L牛血清白蛋白
1g/L Tween80
1g/L叠氮钠;
试剂R2,包括:
MES缓冲液200mM,pH8.0
0.1μg/ml G6PDH-阿米卡星偶联物
100mM NaCl
1g/L牛血清白蛋白
1g/L Tween80
1g/L叠氮钠;
校准品:20mM HEPES缓冲液,以及0μg/ml、3μg/ml、10μg/ml、20μg/ml、35μg/ml、50μg/ml阿米卡星(或按需加入);
质控品:20mM HEPES缓冲液,以及4-5μg/ml、14-16μg/ml、28-32μg/ml阿米卡星(或按需加入)。
将上述试剂(任选包含质控品、校准品),组装成阿米卡星均相酶免疫检测试剂盒。
检测例
均相酶免疫测定的原理:在液体均相反应体系中,酶标记抗原(如G6PDH-阿米卡星)与非标记抗原(阿米卡星),竞争与定量的抗体(阿米卡星抗体)进行结合,当抗体与非标记抗原结合越多,酶标记抗原释放的活性就越多,酶催化底物NAD+生成NADH就越多。
在340nm波长下检测NADH的吸光度变化,即可推算出液体中阿米卡星的含量。
表1.全自动生化仪参数
检测机型 | 雅培C16000 |
分析/时间/读点 | 速率/10min/28-33 |
R1/R2/S | 150:50:3 |
波长(副/主) | 405/340 |
反应类型 | 递增 |
校准类型 | Spine |
校准点 | 6 |
校准品浓度 | 0/3/10/20/35/50 |
检测例1.本申请试剂盒的性能
1.定标实验
表2.阿米卡星检测试剂盒定标吸光度
2.精密度实验
表3.总不精密度
3.重复性
表4.重复性
4.回收测试
表5.回收数据
5.线性实验
表6.线性
/>
检测例2.加速稳定性
本申请试剂(G426突变体)37℃加速7天后,定标吸光度下降小于5%,对照试剂37℃加速7天后,定标吸光度下降显著。
表7.37℃加速稳定性
检测例3.抗体抑制率
1.抗体抑制率的检测原理
当抗体与G6PDH-阿米卡星偶联物结合时,由于空间位阻导致G6PDH酶活性受到影响,从而使得其催化NAD转化为NADH的效率降低,通过检测NADH量的变化,从而比较加入抗体与未加入抗体的实验组的差异,这种差异即体现为抗体对G6PDH的抑制能力。
2.反应体系
表8.抗体抑制率的检测试剂制备
3.结果
比较加入抗体与未加入抗体时,分别检测G6PDH-阿米卡星偶联物吸光度测值,即可得到抗体对G6PDH的抑制情况。
抗体抑制率=(1-含抗体时G6PDH-阿米卡星偶联物的吸光度变化值/不含抗体时G6PDH-阿米卡星的吸光度变化值)×100%。
相对于已发表的突变位点(A45C),本申请的突变体在酶活性保留方面有明显提高,能达到39%以上(G426C:39%;D375C:48%),最高达60%(D306C)。将已发表的突变位点(例如A45C、K55C)参照本申请的方法制备成G6PDH-阿米卡星偶联物,其抑制率仅为32%和38%。
虽然不限于具体理论,但是可以部分地解释为:和现有技术中的G6PDH突变体(A45C、K55C)相比,本申请酶突变体中突变位点(即引入游离巯基的位点)是和半抗原(比如激素、小分子药物等)发生偶联的位置所在。半抗原在这个位置上与半抗原特异性抗体结合时,所构成的空间位阻对G6PDH酶的活性影响最大,同时在引入突变后,还不能实质上影响分子的空间折叠。因此,这个突变位点的位置非常重要,需要同时兼顾G6PDH酶的活性、偶联分子的空间折叠、以及半抗原表位的充分暴露。
由于酶的突变体在抗体抑制率上有明显的提高。将酶的突变体与阿米卡星偶联后的偶联物配制成试剂盒后,试剂在批间变异系数、线性、重复性、稳定性等性能方面有明显的性能提升。
Claims (1)
1.偶联物在制备检测试剂中的用途,其中:
所述检测试剂是阿米卡星的均相酶免疫法检测试剂;
所述偶联物是6-磷酸葡萄糖脱氢酶突变体与阿米卡星衍生物按照摩尔比1:1偶联而成;
所述阿米卡星衍生物是式I所示:
其中,
m为1至10的整数,优选1至5的整数;
更优选,所述阿米卡星衍生物是式II所示:
相较于野生型6-磷酸葡萄糖脱氢酶,所述6-磷酸葡萄糖脱氢酶突变体包含D306C或D375C突变:;
所述6-磷酸葡萄糖脱氢酶突变体是SEQ ID No.2或SEQ ID No.3所示。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2019100177644 | 2019-01-09 | ||
CN201910017764 | 2019-01-09 | ||
CN201910423122.4A CN110174363A (zh) | 2019-01-09 | 2019-05-21 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
CN2019104231224 | 2019-05-21 | ||
CN202010017376.9A CN111537452B (zh) | 2019-01-09 | 2020-01-08 | 6-磷酸葡萄糖脱氢酶突变体及其在制备阿米卡星检测试剂中的用途 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010017376.9A Division CN111537452B (zh) | 2019-01-09 | 2020-01-08 | 6-磷酸葡萄糖脱氢酶突变体及其在制备阿米卡星检测试剂中的用途 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116577494A true CN116577494A (zh) | 2023-08-11 |
Family
ID=67691613
Family Applications (52)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910423122.4A Pending CN110174363A (zh) | 2019-01-09 | 2019-05-21 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
CN201911365439.3A Active CN111239060B (zh) | 2019-01-09 | 2019-12-26 | 6-磷酸葡萄糖脱氢酶突变体及其在制备茶碱检测试剂中的用途 |
CN202310257027.8A Pending CN116144619A (zh) | 2019-01-09 | 2019-12-26 | 茶碱检测试剂盒 |
CN202310217235.5A Pending CN116359146A (zh) | 2019-01-09 | 2019-12-26 | 偶联物的制备方法 |
CN201911372535.0A Active CN112285038B (zh) | 2019-01-09 | 2019-12-27 | 6-磷酸葡萄糖脱氢酶突变体及其在制备洋地黄毒苷检测试剂中的用途 |
CN202310811212.7A Pending CN116735512A (zh) | 2019-01-09 | 2019-12-27 | 偶联物在制备检测试剂中的用途 |
CN202310811210.8A Pending CN116626281A (zh) | 2019-01-09 | 2019-12-27 | 一种洋地黄毒苷检测试剂盒 |
CN202211151264.8A Pending CN116008201A (zh) | 2019-01-09 | 2019-12-27 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
CN202211151405.6A Pending CN115791649A (zh) | 2019-01-09 | 2019-12-27 | 甘胆酸检测试剂盒 |
CN202310811498.9A Pending CN116698772A (zh) | 2019-01-09 | 2019-12-27 | 偶联物的制备方法 |
CN202211153004.4A Pending CN115808398A (zh) | 2019-01-09 | 2019-12-27 | 偶联物的制备方法 |
CN201911372147.2A Active CN112285037B (zh) | 2019-01-09 | 2019-12-27 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
CN202310364997.8A Pending CN116298257A (zh) | 2019-01-09 | 2019-12-31 | 苯妥英检测试剂盒 |
CN202310724066.4A Pending CN116773827A (zh) | 2019-01-09 | 2019-12-31 | 偶联物在制备检测试剂中的用途 |
CN202310365160.5A Pending CN116355873A (zh) | 2019-01-09 | 2019-12-31 | 一种偶联物的制备方法 |
CN202310364266.3A Pending CN116718764A (zh) | 2019-01-09 | 2019-12-31 | 偶联物在制备苯妥英检测试剂中的用途 |
CN201911403882.5A Active CN111650135B (zh) | 2019-01-09 | 2019-12-31 | 6-磷酸葡萄糖脱氢酶突变体及其在制备苯妥英检测试剂中的用途 |
CN201911404154.6A Active CN111504920B (zh) | 2019-01-09 | 2019-12-31 | 6-磷酸葡萄糖脱氢酶突变体及其在制备皮质醇检测试剂中的用途 |
CN202310726498.9A Pending CN116559472A (zh) | 2019-01-09 | 2019-12-31 | 一种皮质醇检测试剂盒 |
CN202310726493.6A Pending CN116773795A (zh) | 2019-01-09 | 2019-12-31 | 一种偶联物的制备方法 |
CN202311025752.9A Pending CN117074335A (zh) | 2019-01-09 | 2020-01-02 | 偶联物在制备检测试剂中的用途 |
CN202010000321.7A Active CN111487206B (zh) | 2019-01-09 | 2020-01-02 | 6-磷酸葡萄糖脱氢酶突变体及其在制备万古霉素检测试剂中的用途 |
CN202311025762.2A Pending CN117054643A (zh) | 2019-01-09 | 2020-01-02 | 万古霉素检测试剂盒 |
CN202311025756.7A Pending CN117030640A (zh) | 2019-01-09 | 2020-01-02 | 偶联物的制备方法 |
CN202010004879.2A Active CN111487207B (zh) | 2019-01-09 | 2020-01-03 | 6-磷酸葡萄糖脱氢酶突变体及其在制备地高辛检测试剂中的用途 |
CN202310810479.4A Pending CN116819060A (zh) | 2019-01-09 | 2020-01-03 | 地高辛检测试剂盒 |
CN202310811497.4A Pending CN116840468A (zh) | 2019-01-09 | 2020-01-03 | 偶联物在制备检测试剂中的用途 |
CN202310810455.9A Pending CN116840467A (zh) | 2019-01-09 | 2020-01-03 | 偶联物的制备方法 |
CN202310452946.0A Pending CN116559425A (zh) | 2019-01-09 | 2020-01-06 | 偶联物在制备检测试剂中的用途 |
CN202310452740.8A Pending CN116430056A (zh) | 2019-01-09 | 2020-01-06 | 偶联物的制备方法 |
CN202010009570.2A Active CN111537451B (zh) | 2019-01-09 | 2020-01-06 | 6-磷酸葡萄糖脱氢酶突变体及其在制备他克莫司检测试剂中的用途 |
CN202310453290.4A Pending CN116338215A (zh) | 2019-01-09 | 2020-01-06 | 他克莫司检测试剂盒 |
CN202310320729.6A Pending CN116297271A (zh) | 2019-01-09 | 2020-01-06 | 偶联物在制备试剂盒中的用途 |
CN202310320137.4A Pending CN116148198A (zh) | 2019-01-09 | 2020-01-06 | 庆大霉素检测试剂的制备方法 |
CN202010009771.2A Active CN111504921B (zh) | 2019-01-09 | 2020-01-06 | 6-磷酸葡萄糖脱氢酶突变体及其在制备庆大霉素检测试剂中的用途 |
CN202310318754.0A Pending CN116124721A (zh) | 2019-01-09 | 2020-01-06 | 庆大霉素检测试剂盒 |
CN202310554774.8A Pending CN116679047A (zh) | 2019-01-09 | 2020-01-07 | 偶联物的制备方法 |
CN202310508217.2A Pending CN116298330A (zh) | 2019-01-09 | 2020-01-07 | 偶联物在制备检测试剂中的用途 |
CN202310553479.0A Pending CN116699125A (zh) | 2019-01-09 | 2020-01-07 | 偶联物在制备检测试剂中的用途 |
CN202010013644.XA Active CN111487208B (zh) | 2019-01-09 | 2020-01-07 | 6-磷酸葡萄糖脱氢酶突变体及其在制备甲氨喋呤检测试剂中的用途 |
CN202310508418.2A Pending CN116381253A (zh) | 2019-01-09 | 2020-01-07 | 偶联物的制备方法 |
CN202310507880.0A Pending CN116754756A (zh) | 2019-01-09 | 2020-01-07 | 甲氨喋呤检测试剂盒 |
CN202310555230.3A Pending CN116718761A (zh) | 2019-01-09 | 2020-01-07 | 环孢霉素a检测试剂盒 |
CN202010013174.7A Active CN111678874B (zh) | 2019-01-09 | 2020-01-07 | 6-磷酸葡萄糖脱氢酶突变体及其在制备环孢霉素a检测试剂中的用途 |
CN202310702870.2A Pending CN116840462A (zh) | 2019-01-09 | 2020-01-08 | 偶联物的制备方法 |
CN202310702860.9A Pending CN116699122A (zh) | 2019-01-09 | 2020-01-08 | 雷帕霉素检测试剂盒 |
CN202310726069.1A Pending CN116754761A (zh) | 2019-01-09 | 2020-01-08 | 阿米卡星检测试剂盒 |
CN202310726230.5A Pending CN116577495A (zh) | 2019-01-09 | 2020-01-08 | 偶联物的制备方法 |
CN202010017376.9A Active CN111537452B (zh) | 2019-01-09 | 2020-01-08 | 6-磷酸葡萄糖脱氢酶突变体及其在制备阿米卡星检测试剂中的用途 |
CN202310725902.0A Pending CN116577494A (zh) | 2019-01-09 | 2020-01-08 | 偶联物在制备检测试剂中的用途 |
CN202310702858.1A Pending CN116859035A (zh) | 2019-01-09 | 2020-01-08 | 偶联物在制备检测试剂中的用途 |
CN202010016535.3A Active CN111693473B (zh) | 2019-01-09 | 2020-01-08 | 6-磷酸葡萄糖脱氢酶突变体及其在制备雷帕霉素检测试剂中的用途 |
Family Applications Before (49)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910423122.4A Pending CN110174363A (zh) | 2019-01-09 | 2019-05-21 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
CN201911365439.3A Active CN111239060B (zh) | 2019-01-09 | 2019-12-26 | 6-磷酸葡萄糖脱氢酶突变体及其在制备茶碱检测试剂中的用途 |
CN202310257027.8A Pending CN116144619A (zh) | 2019-01-09 | 2019-12-26 | 茶碱检测试剂盒 |
CN202310217235.5A Pending CN116359146A (zh) | 2019-01-09 | 2019-12-26 | 偶联物的制备方法 |
CN201911372535.0A Active CN112285038B (zh) | 2019-01-09 | 2019-12-27 | 6-磷酸葡萄糖脱氢酶突变体及其在制备洋地黄毒苷检测试剂中的用途 |
CN202310811212.7A Pending CN116735512A (zh) | 2019-01-09 | 2019-12-27 | 偶联物在制备检测试剂中的用途 |
CN202310811210.8A Pending CN116626281A (zh) | 2019-01-09 | 2019-12-27 | 一种洋地黄毒苷检测试剂盒 |
CN202211151264.8A Pending CN116008201A (zh) | 2019-01-09 | 2019-12-27 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
CN202211151405.6A Pending CN115791649A (zh) | 2019-01-09 | 2019-12-27 | 甘胆酸检测试剂盒 |
CN202310811498.9A Pending CN116698772A (zh) | 2019-01-09 | 2019-12-27 | 偶联物的制备方法 |
CN202211153004.4A Pending CN115808398A (zh) | 2019-01-09 | 2019-12-27 | 偶联物的制备方法 |
CN201911372147.2A Active CN112285037B (zh) | 2019-01-09 | 2019-12-27 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
CN202310364997.8A Pending CN116298257A (zh) | 2019-01-09 | 2019-12-31 | 苯妥英检测试剂盒 |
CN202310724066.4A Pending CN116773827A (zh) | 2019-01-09 | 2019-12-31 | 偶联物在制备检测试剂中的用途 |
CN202310365160.5A Pending CN116355873A (zh) | 2019-01-09 | 2019-12-31 | 一种偶联物的制备方法 |
CN202310364266.3A Pending CN116718764A (zh) | 2019-01-09 | 2019-12-31 | 偶联物在制备苯妥英检测试剂中的用途 |
CN201911403882.5A Active CN111650135B (zh) | 2019-01-09 | 2019-12-31 | 6-磷酸葡萄糖脱氢酶突变体及其在制备苯妥英检测试剂中的用途 |
CN201911404154.6A Active CN111504920B (zh) | 2019-01-09 | 2019-12-31 | 6-磷酸葡萄糖脱氢酶突变体及其在制备皮质醇检测试剂中的用途 |
CN202310726498.9A Pending CN116559472A (zh) | 2019-01-09 | 2019-12-31 | 一种皮质醇检测试剂盒 |
CN202310726493.6A Pending CN116773795A (zh) | 2019-01-09 | 2019-12-31 | 一种偶联物的制备方法 |
CN202311025752.9A Pending CN117074335A (zh) | 2019-01-09 | 2020-01-02 | 偶联物在制备检测试剂中的用途 |
CN202010000321.7A Active CN111487206B (zh) | 2019-01-09 | 2020-01-02 | 6-磷酸葡萄糖脱氢酶突变体及其在制备万古霉素检测试剂中的用途 |
CN202311025762.2A Pending CN117054643A (zh) | 2019-01-09 | 2020-01-02 | 万古霉素检测试剂盒 |
CN202311025756.7A Pending CN117030640A (zh) | 2019-01-09 | 2020-01-02 | 偶联物的制备方法 |
CN202010004879.2A Active CN111487207B (zh) | 2019-01-09 | 2020-01-03 | 6-磷酸葡萄糖脱氢酶突变体及其在制备地高辛检测试剂中的用途 |
CN202310810479.4A Pending CN116819060A (zh) | 2019-01-09 | 2020-01-03 | 地高辛检测试剂盒 |
CN202310811497.4A Pending CN116840468A (zh) | 2019-01-09 | 2020-01-03 | 偶联物在制备检测试剂中的用途 |
CN202310810455.9A Pending CN116840467A (zh) | 2019-01-09 | 2020-01-03 | 偶联物的制备方法 |
CN202310452946.0A Pending CN116559425A (zh) | 2019-01-09 | 2020-01-06 | 偶联物在制备检测试剂中的用途 |
CN202310452740.8A Pending CN116430056A (zh) | 2019-01-09 | 2020-01-06 | 偶联物的制备方法 |
CN202010009570.2A Active CN111537451B (zh) | 2019-01-09 | 2020-01-06 | 6-磷酸葡萄糖脱氢酶突变体及其在制备他克莫司检测试剂中的用途 |
CN202310453290.4A Pending CN116338215A (zh) | 2019-01-09 | 2020-01-06 | 他克莫司检测试剂盒 |
CN202310320729.6A Pending CN116297271A (zh) | 2019-01-09 | 2020-01-06 | 偶联物在制备试剂盒中的用途 |
CN202310320137.4A Pending CN116148198A (zh) | 2019-01-09 | 2020-01-06 | 庆大霉素检测试剂的制备方法 |
CN202010009771.2A Active CN111504921B (zh) | 2019-01-09 | 2020-01-06 | 6-磷酸葡萄糖脱氢酶突变体及其在制备庆大霉素检测试剂中的用途 |
CN202310318754.0A Pending CN116124721A (zh) | 2019-01-09 | 2020-01-06 | 庆大霉素检测试剂盒 |
CN202310554774.8A Pending CN116679047A (zh) | 2019-01-09 | 2020-01-07 | 偶联物的制备方法 |
CN202310508217.2A Pending CN116298330A (zh) | 2019-01-09 | 2020-01-07 | 偶联物在制备检测试剂中的用途 |
CN202310553479.0A Pending CN116699125A (zh) | 2019-01-09 | 2020-01-07 | 偶联物在制备检测试剂中的用途 |
CN202010013644.XA Active CN111487208B (zh) | 2019-01-09 | 2020-01-07 | 6-磷酸葡萄糖脱氢酶突变体及其在制备甲氨喋呤检测试剂中的用途 |
CN202310508418.2A Pending CN116381253A (zh) | 2019-01-09 | 2020-01-07 | 偶联物的制备方法 |
CN202310507880.0A Pending CN116754756A (zh) | 2019-01-09 | 2020-01-07 | 甲氨喋呤检测试剂盒 |
CN202310555230.3A Pending CN116718761A (zh) | 2019-01-09 | 2020-01-07 | 环孢霉素a检测试剂盒 |
CN202010013174.7A Active CN111678874B (zh) | 2019-01-09 | 2020-01-07 | 6-磷酸葡萄糖脱氢酶突变体及其在制备环孢霉素a检测试剂中的用途 |
CN202310702870.2A Pending CN116840462A (zh) | 2019-01-09 | 2020-01-08 | 偶联物的制备方法 |
CN202310702860.9A Pending CN116699122A (zh) | 2019-01-09 | 2020-01-08 | 雷帕霉素检测试剂盒 |
CN202310726069.1A Pending CN116754761A (zh) | 2019-01-09 | 2020-01-08 | 阿米卡星检测试剂盒 |
CN202310726230.5A Pending CN116577495A (zh) | 2019-01-09 | 2020-01-08 | 偶联物的制备方法 |
CN202010017376.9A Active CN111537452B (zh) | 2019-01-09 | 2020-01-08 | 6-磷酸葡萄糖脱氢酶突变体及其在制备阿米卡星检测试剂中的用途 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310702858.1A Pending CN116859035A (zh) | 2019-01-09 | 2020-01-08 | 偶联物在制备检测试剂中的用途 |
CN202010016535.3A Active CN111693473B (zh) | 2019-01-09 | 2020-01-08 | 6-磷酸葡萄糖脱氢酶突变体及其在制备雷帕霉素检测试剂中的用途 |
Country Status (1)
Country | Link |
---|---|
CN (52) | CN110174363A (zh) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110174363A (zh) * | 2019-01-09 | 2019-08-27 | 北京九强生物技术股份有限公司 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
CN113046335B (zh) * | 2019-12-27 | 2023-05-26 | 中国科学院天津工业生物技术研究所 | 一种仿生辅酶偏好性的葡萄糖6-磷酸脱氢酶突变体及其应用 |
WO2021139375A1 (zh) * | 2020-01-07 | 2021-07-15 | 北京九强生物技术股份有限公司 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
CN112114127A (zh) * | 2020-09-09 | 2020-12-22 | 武汉生之源生物科技股份有限公司 | 一种甘胆酸均相酶免疫测定试剂盒及其制备方法和应用 |
CN112225795A (zh) * | 2020-10-14 | 2021-01-15 | 湖南苏阳医疗科技有限公司 | 6-羟基硫酸褪黑素衍生物及其免疫原、特异性抗体的制备方法和应用 |
CN112574969A (zh) * | 2020-12-28 | 2021-03-30 | 郑州伊美诺生物技术有限公司 | G6pdh突变体及其应用 |
CN113567662A (zh) * | 2021-07-08 | 2021-10-29 | 重庆中元汇吉生物技术有限公司 | 一种测定甘胆酸的试剂盒及其制备方法 |
CN113736744B (zh) * | 2021-10-14 | 2023-07-18 | 江南大学 | 洋地黄毒苷单克隆抗体杂交瘤细胞株及其应用 |
CN115236216B (zh) * | 2022-06-07 | 2024-03-01 | 合肥和合医疗科技有限公司 | 高效液相色谱串联质谱检测全血中免疫抑制剂的试剂盒,其制备方法和检测方法 |
Family Cites Families (62)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2116301B1 (zh) * | 1970-12-07 | 1974-08-30 | Brun Lab Sa Le | |
US4190496A (en) * | 1971-05-14 | 1980-02-26 | Syva Company | Homogeneous enzyme assay for antibodies |
US3997525A (en) * | 1974-01-16 | 1976-12-14 | Bio-Tec, Inc. | Tetra-125 iodo-di-tyramine of digitalis derivative and process for making the same |
DE2901218A1 (de) * | 1979-01-13 | 1980-07-17 | Byk Gulden Lomberg Chem Fab | Ung von theophyllin |
JPS5618983A (en) * | 1979-07-25 | 1981-02-23 | Eisai Co Ltd | Theophylline derivative and its preapration |
US4262089A (en) * | 1980-04-07 | 1981-04-14 | Syva Company | Theophylline antigens and antibodies |
US4341866A (en) * | 1980-06-02 | 1982-07-27 | Syva Company | Antienzyme termination in enzyme immunoassays |
JPS57178159A (en) * | 1981-04-27 | 1982-11-02 | Banyu Pharmaceut Co Ltd | Chemical reagent for detection of amicacin and its determination |
US4608336A (en) * | 1981-08-27 | 1986-08-26 | Miles Laboratories, Inc. | #3B theophylline immunoassay employing 9-theophylline reagents |
US4469797A (en) * | 1982-09-23 | 1984-09-04 | Miles Laboratories, Inc. | Digoxigenin immunogens, antibodies, labeled conjugates, and related derivatives |
EP0119767B1 (en) * | 1983-03-11 | 1990-11-22 | FUJIREBIO KABUSHIKI KAISHA also trading as FUJIREBIO INC. | Method of measuring ligands |
IT1199088B (it) * | 1984-03-09 | 1988-12-30 | Miles Italiana | Saggio di legame specifico mediante impiego di anti-g6pdh come marcante |
US4622294A (en) * | 1985-02-08 | 1986-11-11 | Kung Viola T | Liposome immunoassay reagent and method |
US5068198A (en) * | 1986-03-26 | 1991-11-26 | Syntex (U.S.A.) Inc. | Liquid single reagent for assays involving confining gels |
EP0399127A1 (en) * | 1989-05-23 | 1990-11-28 | Pharmacia ENI Diagnostics Inc. | Homogeneous immunochemical method for determining haptens by means of ion selective electrodes |
DE3919915A1 (de) * | 1989-06-19 | 1990-12-20 | Boehringer Mannheim Gmbh | Aminoalkylmaleimide und davon abgeleitete hapten- und antigenderivate sowie konjugate mit peptiden oder proteinen |
JPH0833394B2 (ja) * | 1990-10-03 | 1996-03-29 | 三洋化成工業株式会社 | 酵素標識ハプテンの製法 |
DK0487301T3 (da) * | 1990-11-20 | 2000-09-18 | Dade Behring Marburg Gmbh | Fremgangsmåde til stabilisering af enzymkonjugater |
DE69121844T2 (de) * | 1990-11-20 | 1997-01-23 | Behringwerke Ag | Immunotest für Cyclosporin |
CA2087397A1 (en) * | 1992-01-22 | 1993-07-23 | Kazuhisa Kubotsu | Immunoassay and reagents used therefor |
CA2156397C (en) * | 1993-04-08 | 2007-05-15 | Valerie Quesniaux | Rapamycin assay |
US6455288B1 (en) * | 1993-04-08 | 2002-09-24 | Dade Behring Marburg Gmbh | Homogeneous immunoassays using mutant glucose-6-phosphate dehydrogenases |
US5747352A (en) * | 1994-05-23 | 1998-05-05 | Beckman Instruments, Inc. | Reagents and methods for the rapid and quantitative assay of pharmacological agents |
CN1319105A (zh) * | 1998-10-09 | 2001-10-24 | 伊索技术公司 | 制备针对环孢菌素及其代谢物特异性区域的抗体的方法 |
AUPP751398A0 (en) * | 1998-12-04 | 1999-01-07 | Commonwealth Scientific And Industrial Research Organisation | Methotrexate derivatives |
US7078495B1 (en) * | 1999-08-03 | 2006-07-18 | Dade Behring Inc. | Monoclonal antibodies to tacrolimus and immunoassay methods for tacrolimus |
US6653456B2 (en) * | 2001-07-31 | 2003-11-25 | Roche Diagnostics Corporation | Site-specific aminoglycoside derivatives and their use in immunodiagnostic assays |
US20050176080A1 (en) * | 2004-02-10 | 2005-08-11 | Vani Bodepudi | Hapten, immunogens and derivatives of ascomycin useful for preparation of antibodies and immunoassays |
US20060046273A1 (en) * | 2004-08-27 | 2006-03-02 | Lin-Zhi International Inc. | Homogeneous enzyme immunoassay for oral fluid |
BRPI0517207A (pt) * | 2004-12-17 | 2008-09-30 | Isotechnika Inc | composto isolado, metabólito isolado de ciclo {{(e)- e (z)- (2s,3r,4r)-3-hidróxi-4-metil-2-(metilamino)-6,8-nonadien oil}-l-2-aminobutiril-n-metil-glicil-n-metil-l-leucil-l-v alil-n-metil-l-leucil-l-alanil-d-alanil-n-metil-l-leucil- n-metil-l-leucil-n-metil-l-valil} (isa247) e os sais e solvatos farmaceuticamente aceitáveis dos mesmos, método de preparação de metabólitos de isa247 in vitro, método de produção de um metabólito hidroxilado de isa247, metabólito hidroxilado isolado de isa247, metabólito hidroxilado isolado, método de produção de um metabólito de epóxido de isa247 in vitro, metabólito isolado de epóxido de isa247, metabólito isolado de epóxido, método de produção de um metabólito de diol de isa247 in vitro, metabólito de diol isolado de isa247, metabólito de diol isolado, método de produção de um metabólito de diol de isa247, método de produção de um metabólito de diol de isa247 e composição farmacêutica |
US7189582B2 (en) * | 2005-04-27 | 2007-03-13 | Dade Behring Inc. | Compositions and methods for detection of sirolimus |
JP4746926B2 (ja) * | 2005-06-29 | 2011-08-10 | シスメックス株式会社 | グルコース−6−リン酸脱水素酵素含有試薬及びグルコース−6−リン酸脱水素酵素安定化方法 |
CN101638640B (zh) * | 2009-09-07 | 2011-01-12 | 北京利德曼生化股份有限公司 | 葡萄糖-6-磷酸脱氢酶及其核苷酸序列、重组载体、重组宿主细胞和试剂盒 |
JP2014503197A (ja) * | 2010-11-24 | 2014-02-13 | ディーエイチ テクノロジーズ デベロップメント プライベート リミテッド | グルコース−6−リン酸脱水素酵素のハイスループット、高感度の検出 |
CN102565399B (zh) * | 2010-12-07 | 2015-06-03 | 北京望尔生物技术有限公司 | 一种检测氢化可的松的方法及其专用酶联免疫试剂盒 |
CN102807618A (zh) * | 2011-08-10 | 2012-12-05 | 重庆金域医学检验所有限公司 | 苯妥因均相酶免疫检测试剂盒及其多克隆抗体的制备方法 |
JP5896375B2 (ja) * | 2011-09-09 | 2016-03-30 | 池田食研株式会社 | 改変型グルコース脱水素酵素遺伝子 |
CN102424829B (zh) * | 2011-10-26 | 2013-10-16 | 苏州汉酶生物技术有限公司 | 一种酶催化合成坦西莫司的方法 |
US8771964B2 (en) * | 2012-02-02 | 2014-07-08 | Siemens Healthcare Diagnostics Inc. | Compositions and methods for detection of methadone metabolite |
KR20150023729A (ko) * | 2012-06-14 | 2015-03-05 | 암브룩스, 인코포레이티드 | 핵 수용체 리간드 폴리펩티드에 접합된 항-psma 항체 |
CN103242446A (zh) * | 2012-07-25 | 2013-08-14 | 苏州博源医疗科技有限公司 | 茶碱免疫原及其制备方法和应用 |
CN102757391B (zh) * | 2012-08-01 | 2015-08-26 | 苏州博源医疗科技有限公司 | 一种***衍生物及其制备方法和应用 |
WO2015094852A2 (en) * | 2013-12-17 | 2015-06-25 | Siemens Healthcare Diagnostics Inc. | Preparation of multi-hapten mutant g6pdh conjugates and their use for detection of multiple analytes |
CN104016923B (zh) * | 2014-01-08 | 2016-08-31 | 南开大学 | 苯妥英衍生物及其制备方法和用途 |
CN103760348B (zh) * | 2014-02-11 | 2015-03-11 | 苏州博源医疗科技有限公司 | 一种甘胆酸免疫检测试剂及其制备和检测方法 |
CN103739703B (zh) * | 2014-02-11 | 2015-07-15 | 苏州博源医疗科技有限公司 | 甘胆酸免疫原、抗甘胆酸特异性抗体及检测试剂 |
JP6398295B2 (ja) * | 2014-04-30 | 2018-10-03 | ニプロ株式会社 | 変異型グルコース−6−リン酸脱水素酵素 |
CN104447745B (zh) * | 2014-11-06 | 2016-03-30 | 济南金域医学检验中心有限公司 | 一种茶碱均相酶免疫检测验试剂盒及其制备方法 |
CN104569373B (zh) * | 2015-01-27 | 2016-08-17 | 苏州博源医疗科技有限公司 | 一种甲氨蝶呤均相酶免疫检测试剂及其制备和检测方法 |
CN107636170A (zh) * | 2015-02-04 | 2018-01-26 | 健泰科生物技术公司 | 突变型Smoothened及其使用方法 |
CN105131105A (zh) * | 2015-07-27 | 2015-12-09 | 苏州博源医疗科技有限公司 | 皮质醇免疫原、衍生物、抗体、检测试剂及制备方法 |
CN106565809B (zh) * | 2016-07-08 | 2018-05-01 | 北京九强生物技术股份有限公司 | 一种β半乳糖苷酶的酶供体偶联物及其在甘胆酸检测中的用途 |
CN106226512B (zh) * | 2016-07-29 | 2018-10-16 | 胡清 | 一种试剂盒、试剂盒的制备方法及利用该试剂盒实现的外周血甘氨胆酸的检测方法 |
CN106190996B (zh) * | 2016-08-30 | 2019-05-21 | 美康生物科技股份有限公司 | 一种葡萄糖6磷酸脱氢酶突变体 |
CN109797143B (zh) * | 2016-09-22 | 2021-02-12 | 北京九强生物技术股份有限公司 | 一种包含大肠杆菌β半乳糖苷酶受体的试剂 |
CN106872681B (zh) * | 2017-01-23 | 2019-11-19 | 四川精卫食品检测科技有限公司 | 丁胺卡那霉素和卡那霉素二合一快速检测酶联免疫试剂盒及其应用 |
CN108593905A (zh) * | 2017-12-22 | 2018-09-28 | 太原瑞盛生物科技有限公司 | 一种地高辛免疫检测试剂及其制备和检测方法 |
CN108586562B (zh) * | 2018-05-08 | 2019-09-06 | 苏州博源医疗科技有限公司 | 一种皮质醇衍生物及其制备方法与应用 |
CN108717117A (zh) * | 2018-05-23 | 2018-10-30 | 太原瑞盛生物科技有限公司 | 一种万古霉素免疫检测试剂及其制备和检测方法 |
CN109111494A (zh) * | 2018-08-30 | 2019-01-01 | 苏州博源医疗科技有限公司 | ***衍生物、免疫原、抗体、酶标偶联物、检测试剂及其制备方法 |
CN110174363A (zh) * | 2019-01-09 | 2019-08-27 | 北京九强生物技术股份有限公司 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
CN112574969A (zh) * | 2020-12-28 | 2021-03-30 | 郑州伊美诺生物技术有限公司 | G6pdh突变体及其应用 |
-
2019
- 2019-05-21 CN CN201910423122.4A patent/CN110174363A/zh active Pending
- 2019-12-26 CN CN201911365439.3A patent/CN111239060B/zh active Active
- 2019-12-26 CN CN202310257027.8A patent/CN116144619A/zh active Pending
- 2019-12-26 CN CN202310217235.5A patent/CN116359146A/zh active Pending
- 2019-12-27 CN CN201911372535.0A patent/CN112285038B/zh active Active
- 2019-12-27 CN CN202310811212.7A patent/CN116735512A/zh active Pending
- 2019-12-27 CN CN202310811210.8A patent/CN116626281A/zh active Pending
- 2019-12-27 CN CN202211151264.8A patent/CN116008201A/zh active Pending
- 2019-12-27 CN CN202211151405.6A patent/CN115791649A/zh active Pending
- 2019-12-27 CN CN202310811498.9A patent/CN116698772A/zh active Pending
- 2019-12-27 CN CN202211153004.4A patent/CN115808398A/zh active Pending
- 2019-12-27 CN CN201911372147.2A patent/CN112285037B/zh active Active
- 2019-12-31 CN CN202310364997.8A patent/CN116298257A/zh active Pending
- 2019-12-31 CN CN202310724066.4A patent/CN116773827A/zh active Pending
- 2019-12-31 CN CN202310365160.5A patent/CN116355873A/zh active Pending
- 2019-12-31 CN CN202310364266.3A patent/CN116718764A/zh active Pending
- 2019-12-31 CN CN201911403882.5A patent/CN111650135B/zh active Active
- 2019-12-31 CN CN201911404154.6A patent/CN111504920B/zh active Active
- 2019-12-31 CN CN202310726498.9A patent/CN116559472A/zh active Pending
- 2019-12-31 CN CN202310726493.6A patent/CN116773795A/zh active Pending
-
2020
- 2020-01-02 CN CN202311025752.9A patent/CN117074335A/zh active Pending
- 2020-01-02 CN CN202010000321.7A patent/CN111487206B/zh active Active
- 2020-01-02 CN CN202311025762.2A patent/CN117054643A/zh active Pending
- 2020-01-02 CN CN202311025756.7A patent/CN117030640A/zh active Pending
- 2020-01-03 CN CN202010004879.2A patent/CN111487207B/zh active Active
- 2020-01-03 CN CN202310810479.4A patent/CN116819060A/zh active Pending
- 2020-01-03 CN CN202310811497.4A patent/CN116840468A/zh active Pending
- 2020-01-03 CN CN202310810455.9A patent/CN116840467A/zh active Pending
- 2020-01-06 CN CN202310452946.0A patent/CN116559425A/zh active Pending
- 2020-01-06 CN CN202310452740.8A patent/CN116430056A/zh active Pending
- 2020-01-06 CN CN202010009570.2A patent/CN111537451B/zh active Active
- 2020-01-06 CN CN202310453290.4A patent/CN116338215A/zh active Pending
- 2020-01-06 CN CN202310320729.6A patent/CN116297271A/zh active Pending
- 2020-01-06 CN CN202310320137.4A patent/CN116148198A/zh active Pending
- 2020-01-06 CN CN202010009771.2A patent/CN111504921B/zh active Active
- 2020-01-06 CN CN202310318754.0A patent/CN116124721A/zh active Pending
- 2020-01-07 CN CN202310554774.8A patent/CN116679047A/zh active Pending
- 2020-01-07 CN CN202310508217.2A patent/CN116298330A/zh active Pending
- 2020-01-07 CN CN202310553479.0A patent/CN116699125A/zh active Pending
- 2020-01-07 CN CN202010013644.XA patent/CN111487208B/zh active Active
- 2020-01-07 CN CN202310508418.2A patent/CN116381253A/zh active Pending
- 2020-01-07 CN CN202310507880.0A patent/CN116754756A/zh active Pending
- 2020-01-07 CN CN202310555230.3A patent/CN116718761A/zh active Pending
- 2020-01-07 CN CN202010013174.7A patent/CN111678874B/zh active Active
- 2020-01-08 CN CN202310702870.2A patent/CN116840462A/zh active Pending
- 2020-01-08 CN CN202310702860.9A patent/CN116699122A/zh active Pending
- 2020-01-08 CN CN202310726069.1A patent/CN116754761A/zh active Pending
- 2020-01-08 CN CN202310726230.5A patent/CN116577495A/zh active Pending
- 2020-01-08 CN CN202010017376.9A patent/CN111537452B/zh active Active
- 2020-01-08 CN CN202310725902.0A patent/CN116577494A/zh active Pending
- 2020-01-08 CN CN202310702858.1A patent/CN116859035A/zh active Pending
- 2020-01-08 CN CN202010016535.3A patent/CN111693473B/zh active Active
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111537452B (zh) | 6-磷酸葡萄糖脱氢酶突变体及其在制备阿米卡星检测试剂中的用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |