WO2021187531A1 - 発光基質化合物 - Google Patents

発光基質化合物 Download PDF

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WO2021187531A1
WO2021187531A1 PCT/JP2021/010852 JP2021010852W WO2021187531A1 WO 2021187531 A1 WO2021187531 A1 WO 2021187531A1 JP 2021010852 W JP2021010852 W JP 2021010852W WO 2021187531 A1 WO2021187531 A1 WO 2021187531A1
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group
formula
salt
solvate
hydrate
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French (fr)
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諒 西原
僚二 栗田
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National Institute of Advanced Industrial Science and Technology AIST
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    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • 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
    • 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
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks

Definitions

  • the present invention relates to a compound serving as a luminescent substrate and its use.
  • protein analysis technology has a wide variety of detection methods depending on the application, such as an ultraviolet absorptiometry method utilizing an ultraviolet light absorption characteristic of 280 nm and a BCA method for detecting by reduction of copper.
  • these methods are detrimental to other biomolecules such as nucleic acids and phospholipids.
  • protein analysis by the fluorescence method is relatively sensitive, but the excitation light source at the time of observation induces a high background signal. Therefore, the current protein analysis technique is time inefficient in addition to complicated operations such as sample pretreatment.
  • the fluorescence method is unsuitable for continuous observation of protein dynamics in a living body because its excitation light source may cause protein denaturation and phototoxicity.
  • HSA human serum albumin
  • R 1 is -CH 2 -A (where A is hydrogen, or the following formula: (During the ceremony, R 3 is hydrogen, hydroxyl group, fluorine, an alkyl group having 1 to 5 carbon atoms, a methoxy group, or a trifluoromethyl group, and m is an integer of 0 to 5. ) Group represented by, or the following formula: It is a group represented by.
  • R 2 is the following formula: (In the formula, R 4 is (i) -O- (CH 2 ) n -R 6 (where R 6 is a hydroxyl group, a methoxy group, a methyl group, a trifluoromethyl group or an azide group, and n is an integer of 1 to 5. ), (ii) Alkyl group having 1 to 5 carbon atoms, or (iii) The following formula: It is one of the groups represented by.
  • R 5 is (i) Hydrogen atom, hydroxyl group, methoxy group, methyl group, trifluoromethyl group, dimethylamino group, phenyl group, or azide group, (ii) Alkyl groups with 1 to 5 carbon atoms, (iii) -O- (CH 2 ) p -R 7 (Here, R 7 is a hydroxyl group, a methoxy group, a methyl group, a trifluoromethyl group, a dimethylamino group, an azide group, or an alkyl having 1 to 5 carbon atoms.
  • the compound represented by the formula [I] is the following formula [II]: [In formula [II], R 3 is a hydrogen, a hydroxyl group, a fluorine, an alkyl group having 1 to 5 carbon atoms, a methoxy group, or a trifluoromethyl group. R 4 is (i) -O- (CH 2 ) n -R 6 (where R 6 is a hydroxyl group, a methoxy group, a methyl group, a trifluoromethyl group or an azide group, and n is an integer of 1 to 5. ), (ii) Alkyl group having 1 to 5 carbon atoms, or (iii) The following formula: It is a group represented by any one of them. ] The compound according to (1) above, a salt thereof, or a hydrate or solvate thereof, which is a compound represented by.
  • the compound represented by the formula [I] is the following formula [III]: [In formula [III], R 4 is (i) -O- (CH 2 ) n -R 6 (where R 6 is a hydroxyl group, a methoxy group, a methyl group, a trifluoromethyl group or an azide group, and n is an integer of 1 to 5. ), (ii) Alkyl group having 1 to 5 carbon atoms, or (iii) The following formula: It is a group represented by any one of them. ] The compound according to (1) above, a salt thereof, or a hydrate or solvate thereof, which is a compound represented by.
  • R 3 is a hydrogen, a hydroxyl group, a fluorine, an alkyl group having 1 to 5 carbon atoms, a methoxy group, or a trifluoromethyl group.
  • R 5 is (i) Hydrogen atom, hydroxyl group, methoxy group, methyl group, trifluoromethyl group, dimethylamino group, phenyl group, or azide group, (ii) Alkyl groups with 1 to 5 carbon atoms, (iii) -O- (CH 2 ) p -R 7 (Here, R 7 is a hydroxyl group, a methoxy group, a methyl group, a trifluoromethyl group, a dimethylamino group, an azide group, or an alkyl having 1 to 5 carbon atoms.
  • a luminescent substrate for a protein or peptide which comprises the compound according to any one of (1) to (14) above, a salt thereof, or a hydrate or solvate thereof.
  • the compound according to any one of (1) to (14) above, or a salt thereof, or a hydrate or solvate thereof, or the luminescent substrate of (15) above is administered in vivo.
  • a method for analyzing a protein or peptide which comprises adding in vitro to detect the desired protein or peptide.
  • a novel compound or the like as a luminescent molecule (a luminescent substrate that produces light by an enzymatic reaction with a human-derived protein) that serves as a substrate for a human-derived protein. Since the compounds of the present invention have higher luminescence intensity than known luminescent substrate compounds such as coelenterazine derivatives, proteins capable of performing quantitative analysis of desired proteins in solutions having various compositions easily and with high sensitivity. It is extremely useful and practical in the development of analytical technology.
  • FIG. 1 It is a figure which shows the luminescence intensity with human or bovine serum albumin of each compound of an Example and a comparative example of this invention. It is a figure which shows the luminescence intensity with each human-derived protein or bovine serum albumin of the compound (HuLumino12) of the Example of this invention.
  • a is a schematic diagram. It is a figure which shows the luminescence property (signal to noise ratio, S / N ratio) in human serum albumin (HSA) of each compound of an Example and a comparative example of this invention. It is a figure which shows the luminescence property (luminescence duration) in human serum albumin (HSA) of the compound (HuLumino12) of the Example of this invention.
  • a luminescent molecule contained in a luminescent organism and composed of amino acids is utilized as a chemical probe for converting molecular recognition or enzymatic reaction into spectroscopic information.
  • Bioanalysis utilizing these luminescence reactions enables trace analysis and bioimaging that do not require an excitation light source, and is widely used as a highly sensitive analysis technique in life science. This is due to the fact that luminescent molecules use chemical reactions for excitation energy.
  • Luminescent systems widely used for bioanalysis include marine luminescent species such as firefly luminescent system and luminescent Aequorea coeruleus.
  • the renilla-luciferase (RLuc) luminescence system which is one of the marine luminescent species and uses coelenterazine (CTZ) as the luminescent substrate, is a simple luminescent system that does not require any cofactors other than oxygen molecules (for details, see CTZ. It is a simple luminescence mechanism that emits light with the movement of protons in the chemical structure), and enables highly reproducible analysis not only inside the cell but also outside the cell where ATP does not exist. Therefore, many CTZ derivatives in which the chemical structure of CTZ has been modified have been reported so far, and their optical properties have been investigated in detail (Patent Documents 1 and 2 and Non-Patent Documents 3 and 4 described above).
  • the compound according to the present invention is a compound as a luminescent molecule (a luminescent substrate that produces light by an enzymatic reaction with a human-derived protein) that serves as a substrate for a human-derived protein, and is more than a known luminescent substrate compound as described above. It was found as a compound having high luminescence intensity and excellent usefulness and practicality.
  • Luminescent Substrate Compound The compound according to the present invention (hereinafter, also referred to as the compound of the present invention) is a compound represented by the following formula [I].
  • R 1 is -CH 2 -A.
  • the above A is hydrogen, or the following formula:
  • R 3 is hydrogen, hydroxyl group, fluorine, an alkyl group having 1 to 5 carbon atoms, a methoxy group, or a trifluoromethyl group, and m is an integer of 0 to 5.
  • R 2 is the following formula: (In the formula, R 4 is (i) -O- (CH 2 ) n -R 6 (where R 6 is a hydroxyl group, a methoxy group, a methyl group, a trifluoromethyl group or an azide group, and n is an integer of 1 to 5. ), (ii) Alkyl group having 1 to 5 carbon atoms, or (iii) The following formula: It is one of the groups represented by.
  • R 5 is (i) Hydrogen atom, hydroxyl group, methoxy group, methyl group, trifluoromethyl group, dimethylamino group, phenyl group, or azide group, (ii) Alkyl groups with 1 to 5 carbon atoms, (iii) -O- (CH 2 ) p -R 7 (Here, R 7 is a hydroxyl group, a methoxy group, a methyl group, a trifluoromethyl group, a dimethylamino group, an azide group, or an alkyl having 1 to 5 carbon atoms. It is a group, and p is an integer from 1 to 5.) Or (iv) The following equation: It is one of the groups represented by, and n is an integer from 0 to 5. ) It is a group represented by.
  • the compound represented by the formula [I] is not limited, but is represented by a compound represented by the following formula [II], a compound represented by the following formula [III], and a compound represented by the following formula [IV]. Compounds and the like are preferably mentioned.
  • R 4 is not limited, but the ones described in the following table are preferably mentioned, for example.
  • n and R 3 and R 5 are not limited, but the ones described in the following table are preferably mentioned, for example.
  • a salt of the compound preferably, for example, a pharmacologically acceptable salt
  • Such salts include, but are not limited to, for example, hydrohalogenates (eg, hydrochlorides, hydrobromide, and hydroiodide), inorganic salts (eg, sulfates, nitrates, etc.).
  • Preferable examples include acid salts and glutamates), quaternary amine salts, alkali metal salts (eg, sodium salts and potassium salts, etc.), alkaline earth metal salts (eg, magnesium salts, calcium salts, etc.) and the like. ..
  • the compound of the present invention includes all isomers that can occur due to the structure of the compound (for example, geometric isomers, optical isomers based on asymmetric carbon, rotational isomers, stereoisomers, homomorphs, etc.). And a mixture of two or more kinds of these isomers is also included, and the description is not limited to the description of the structural formula for convenience.
  • the compound of the present invention may be any of S-form, R-form and RS-form, and is not limited.
  • the compound of the present invention may exist in the form of a hydrate or a solvate depending on the type thereof, and in the present invention, the hydrate and the solvate are also included in the compound of the present invention. It can be used for the same purpose as the compound of.
  • the solvate is not limited, and examples thereof include a solvate with ethanol.
  • the compound of the present invention is, for example, a ketoacetal compound (in the formula, R 3a is a TBS (t-butyldimethylsilyl) protected hydroxyl group or hydrogen) as shown in the following reaction scheme 1.
  • a coelenteramine derivative in the formula, R 4 has the same meaning as above, the same applies hereinafter) can be produced.
  • a coelenteramine derivative used as a starting material which is used for producing a compound in which R 4 in the formula [II] is an alkyl group having 1 to 5 carbon atoms, is, for example, It can be produced by the following reaction scheme 3.
  • the compound of the present invention can be used as a luminescent substrate for a desired protein or peptide.
  • the desired protein or peptide include, but are not limited to, those derived from humans.
  • the desired protein or peptide is, for example, but not limited to, for example, a luciferase enzyme (for example, RLuc8 of a luciferase (RLuc) luminescent system (reference: Loening, A. M. et al., Protein Eng. Des). .Sel., 2006, 19, 391-400 .; Loening, A. M. et al., J. Mol. Biol., 2007, 374, 1017-1028 .; Loening, A. M. et al., Protein Eng.
  • a luciferase enzyme for example, RLuc8 of a luciferase (RLuc) luminescent system
  • the compound of the present invention can also be used in a method for analyzing a protein or peptide, which comprises detecting a desired protein or peptide by administering it in vivo or adding it in vitro.
  • a protein or peptide those derived from humans are preferably mentioned, and specifically, the above-mentioned description can be applied.
  • the in vivo administration method / administration conditions and the in vitro addition method / addition conditions are not particularly limited, and should be appropriately selected / set with reference to generally known well-known methods / conditions. Can be done.
  • the protein or peptide may be detected as long as it is a method capable of detecting luminescence derived from the compound of the present invention as a luminescent molecule, and a well-known detection device or detection conditions can be set, and there are no particular restrictions. Not done.
  • the reaction solution was evacuated, a catalytic amount of tetrakistriphenylphosphine palladium (0) (about 1 tablespoon of microspatula) was added, the reaction solution was evacuated again, and the mixture was stirred at 100 ° C. overnight (12 hours). After allowing to cool to room temperature, the palladium catalyst was removed by filtration through Celite. The obtained residue was extracted with ethyl acetate, washed with distilled water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure.
  • the reaction solution was evacuated, a catalytic amount of tetrakistriphenylphosphine palladium (0) (about 1 tablespoon of microspatula) was added, the reaction solution was evacuated again, and the mixture was stirred at 100 ° C. overnight (12 hours). After allowing to cool to room temperature, the palladium catalyst was removed by filtration through Celite. The obtained residue was extracted with ethyl acetate, washed with distilled water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure.
  • NCTZ Native CTZ; Fujifilm Wako Pure Chemical Industries, Ltd.
  • DeepBlueC TM NanoLight
  • MCLA TM Cayman Chemical
  • BBlue2.3 Non-Patent Document 4: R. Nishihara et al. Represented by the following structural formulas. , Theranostics, 2019, 9, 2646-2661.), Each of which was used as a compound according to Comparative Examples 1 to 4.
  • Comparative Examples 1 to 3 represented by the following structural formulas (see Non-Patent Document 3: T. Hirono et al., Tetrahedron Letters, 1992, 33, 5771-5774.) Are shown in Comparative Example 5 in order. The compounds according to 7 to 7 were used.
  • the reaction solution was evacuated, a catalytic amount of tetrakistriphenylphosphine palladium (0) (about 1 tablespoon of microspatula) was added, the reaction solution was evacuated again, and the mixture was stirred at 100 ° C. overnight. After allowing to cool to room temperature, the palladium catalyst was removed by filtration through Celite. The obtained residue was extracted with ethyl acetate, washed with distilled water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure.
  • the reaction solution was evacuated, a catalytic amount of tetrakistriphenylphosphine palladium (0) (about 1 tablespoon of microspatula) was added, the reaction solution was evacuated again, and the mixture was stirred at 100 ° C. overnight. After allowing to cool to room temperature, the palladium catalyst was removed by filtration through Celite. The obtained residue was extracted with ethyl acetate, washed with distilled water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure.
  • the reaction solution was evacuated, a catalytic amount of tetrakistriphenylphosphine palladium (0) (about 1 tablespoon of microspatula) was added, the reaction solution was evacuated again, and the mixture was stirred at 100 ° C. overnight. After allowing to cool to room temperature, the palladium catalyst was removed by filtration through Celite. The obtained residue was extracted with ethyl acetate, washed with distilled water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure.
  • the novel compound of the present invention was recognized by human serum albumin (HSA) and showed significant luminescence.
  • HSA human serum albumin
  • the combination of HuLumino 12 / HSA was found to have 912 times the emission intensity of NCTZ / HSA.
  • the HuLumino 12 / HSA and NCTZ / HSA Michaelis-Menten constants are 4.2 ⁇ M and 25.3 ⁇ M, respectively, and the luminescent molecule of the present invention has a higher affinity for HSA than the conventional molecule.
  • HuLumino32 which has a relatively high fluorescence quantum yield, showed the highest emission intensity in both BSA and HSA.
  • Emission spectrum measurement method When the emission spectrum was measured in the same manner as in the above emission intensity measurement method, it was found that the maximum emission wavelength was 427 nm (FIG. 6). The emission spectrum was measured using a spectroscopic measuring device. The maximum emission wavelength was obtained by standardizing the maximum emission intensity as 1.0.
  • the design of the CTZ derivative obtained in the present invention can also be applied to other bioluminescent systems.
  • the thorny shrimp (Oplophorus gracilirostris) uses CTZ as a luminescent substrate.
  • luciferase NanoLuc (trade name) (Promega) derived from spiny shrimp has been developed (reference: Hall P. M. et al., ACS. Chem. Biol., 2012, 7, 1848-1857.). When combined with the substrate furimazine, it has about 100 times the luminescence intensity of the firefly luciferase luminescence system.
  • the compound of the present invention can be used not only for detecting human-derived proteins, but also as a reagent for detecting structural deterioration and aggregates of antibody proteins by luminescence. It can be used for quality control of antibody drugs and immunochromatographic in vitro diagnostic agents. Further, the binding property between the serum protein and the drug can be rapidly determined by conducting a competitive inhibition test with the compound of the present invention which is a luminescent molecule. Therefore, the compound of the present invention contributes to the acceleration of drug discovery research as one of the pharmacokinetic evaluation methods.

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024262411A1 (ja) * 2023-06-22 2024-12-26 国立研究開発法人産業技術総合研究所 血清アルブミンの検出剤
WO2025084165A1 (ja) * 2023-10-18 2025-04-24 国立研究開発法人産業技術総合研究所 抗体の変性状態の評価方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118084918A (zh) * 2024-01-29 2024-05-28 中国药科大学 一种化学发光探针及其制备方法和在检测β淀粉样蛋白中的应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018158896A (ja) * 2017-03-22 2018-10-11 学校法人慶應義塾 新規セレンテラジン化合物及びその用途
JP2018165265A (ja) * 2017-03-28 2018-10-25 国立大学法人電気通信大学 新規セレンテラジン誘導体

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0560697A (ja) * 1991-08-30 1993-03-12 Nippon Oil & Fats Co Ltd スーパーオキシドアニオンの定量方法及びスーパーオキシドアニオン消去物質の定量方法
CN106148362B (zh) * 2010-11-02 2021-04-30 普罗梅加公司 新型腔肠素底物及其使用方法
US9849198B2 (en) * 2013-07-02 2017-12-26 The Board Of Trustees Of The Leland Stanford Junior University Discrete imaging of hepatic oxidative and nitrosative stress with two-channel nanoparticles for in vivo drug safety screening

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018158896A (ja) * 2017-03-22 2018-10-11 学校法人慶應義塾 新規セレンテラジン化合物及びその用途
JP2018165265A (ja) * 2017-03-28 2018-10-25 国立大学法人電気通信大学 新規セレンテラジン誘導体

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
HIRANO TAKASHI ET AL: "Chemiluminescence of coelenterazine analogues: Structures of emitting species", TETRAHEDRON LETTERS, ELSEVIER, AMSTERDAM , NL, vol. 33, no. 39, 1 January 1992 (1992-01-01), Amsterdam , NL , pages 5771 - 5774, XP002444903, ISSN: 0040-4039, DOI: 10.1016/0040-4039(92)89028-B *
KUBOTA, HIDEHIRO: "Development of a convenient and highly sensitive antioxidant capacity assay for food ingredients", TECHNICAL REPORT OF JAPAN FOOD INDUSTRY CENTER, vol. 27, 2001, pages 47 - 56, ISSN: 0388-3388 *
NISHIHARA RYO, NIWA KAZUKI, TOMITA TATSUNOSUKE, KURITA RYOJI: "Coelenterazine Analogue with Human Serum Albumin-Specific Bioluminescence", BIOCONJUG CHEM, vol. 31, no. 12, 16 December 2020 (2020-12-16), pages 2679 - 2684, XP055859050 *
NISHIHARA RYO, PAULMURUGAN RAMASAMY, NAKAJIMA TAKAHIRO, YAMAMOTO EIJI, NATARAJAN ARUTSELVAN, AFJEI RAYHANEH, HIRUTA YUKI, IWASAWA : "Highly bright and stable NIR-BRET with blue-shifted coelenterazine derivatives for deep-tissue imaging of molecular events in vivo", THERANOSTICS, vol. 9, no. 9, 13 April 2019 (2019-04-13), pages 2646 - 2661, XP055859049 *
VASSEL N, COX CD, NASEEM R, MORSE V, EVANS RT, POWER RL, BRANCALE A, WANN KT, CAMPBELL AK: "Enzymatic activity of albumin shown by coelenterazine chemiluminescence", LUMINESCENCE, vol. 27, no. 3, May 2012 (2012-05-01), pages 234 - 241, XP055859048 *
YANG JING, YIN WEI, YIN KEYI, WANG PENG, ZHENG CHAO, ZHU BIYUE, RAN KATHLEEN, ZHANG CAN, SHAO YIHAN, RAN CHONGZHAO: "Smart chemiluminescence probes and dual-amplification of signal for detection of amyloid beta species in Alzheimer's disease model", CHEMRXIV, 17 April 2020 (2020-04-17), pages 1 - 25, XP055859051 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024262411A1 (ja) * 2023-06-22 2024-12-26 国立研究開発法人産業技術総合研究所 血清アルブミンの検出剤
WO2025084165A1 (ja) * 2023-10-18 2025-04-24 国立研究開発法人産業技術総合研究所 抗体の変性状態の評価方法

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