EP1021462A1 - Essais pour ligands a recepteurs nucleaires reposant sur le transfert d'energie de resonance en fluorescence - Google Patents

Essais pour ligands a recepteurs nucleaires reposant sur le transfert d'energie de resonance en fluorescence

Info

Publication number
EP1021462A1
EP1021462A1 EP98956094A EP98956094A EP1021462A1 EP 1021462 A1 EP1021462 A1 EP 1021462A1 EP 98956094 A EP98956094 A EP 98956094A EP 98956094 A EP98956094 A EP 98956094A EP 1021462 A1 EP1021462 A1 EP 1021462A1
Authority
EP
European Patent Office
Prior art keywords
nuclear receptor
binding domain
ligand binding
cbp
human
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.)
Withdrawn
Application number
EP98956094A
Other languages
German (de)
English (en)
Other versions
EP1021462A4 (fr
Inventor
Richard T. Cummings
Jeffrey D. Hermes
David E. Moller
Gaochao Zhou
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Original Assignee
Merck and Co Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Merck and Co Inc filed Critical Merck and Co Inc
Publication of EP1021462A1 publication Critical patent/EP1021462A1/fr
Publication of EP1021462A4 publication Critical patent/EP1021462A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • 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
    • G01N33/536—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase
    • G01N33/542—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
    • 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
    • G01N33/566—Immunoassay; Biospecific binding assay; Materials therefor using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
    • 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
    • G01N33/6875—Nucleoproteins
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70567—Nuclear receptors, e.g. retinoic acid receptor [RAR], RXR, nuclear orphan receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value

Definitions

  • the nuclear receptor co-activator is human SRC-1 and the binding portion includes a contiguous stretch of amino acids of human SRC-1 selected from the group consisting of: positions 45-53, 632-640, 689-696, 748-755, and 1434-1441.
  • a nuclear receptor or ligand binding domain thereof labeled with a first fluorescent reagent (a) a nuclear receptor or ligand binding domain thereof labeled with a first fluorescent reagent; (b) CBP, p300, or other nuclear receptor co-activator, or a binding portion thereof, labeled with a second fluorescent reagent; (c) an agonist of the nuclear receptor; and
  • FRET donor-acceptor pairs are suitable for the practice of the present invention.
  • the following donor- acceptor pairs can be used: dansyl/fluorescein; fluorescein/rhodamine; tryptophan/aminocoumarin.
  • Human PPAR ⁇ 2 contains the same amino acid sequence as human PPAR ⁇ l except for an amino terminal addition of 24 amino acids (see Elbrecht et al., 1996, Biochem. Biophys. Res. Comm. 224:431-437).
  • hCBPl-113 was directly labeled with europium cryptate (Eu3+K); hPPAR ⁇ lLBD was indirectly labeled with

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Cell Biology (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un procédé permettant d'identifier des agonistes et des antagonistes vis-à-vis de récepteurs nucléaires, qui consiste à mesurer le transfert d'énergie de résonance en fluorescence entre un récepteur nucléaire ou un domaine de liaison marqué par fluorescence et une protéine se liant au CRE, p300, un autre co-activateur nucléaire ou une partie de liaison qui lui appartient. Le procédé est simple, rapide, et peu onéreux. L'invention concerne également des récepteurs nucléaires et des co-activateurs de ces récepteurs marqués au moyen de réactifs fluorescents, qui sont destinés à être utilisés aux fins du procédé considéré.
EP98956094A 1997-10-07 1998-10-06 Essais pour ligands a recepteurs nucleaires reposant sur le transfert d'energie de resonance en fluorescence Withdrawn EP1021462A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US6138597P 1997-10-07 1997-10-07
US61385P 1997-10-07
PCT/US1998/021049 WO1999018124A1 (fr) 1997-10-07 1998-10-06 Essais pour ligands a recepteurs nucleaires reposant sur le transfert d'energie de resonance en fluorescence

Publications (2)

Publication Number Publication Date
EP1021462A1 true EP1021462A1 (fr) 2000-07-26
EP1021462A4 EP1021462A4 (fr) 2005-04-13

Family

ID=22035450

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98956094A Withdrawn EP1021462A4 (fr) 1997-10-07 1998-10-06 Essais pour ligands a recepteurs nucleaires reposant sur le transfert d'energie de resonance en fluorescence

Country Status (4)

Country Link
EP (1) EP1021462A4 (fr)
JP (1) JP2001519525A (fr)
CA (1) CA2305711A1 (fr)
WO (1) WO1999018124A1 (fr)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002528721A (ja) * 1998-10-23 2002-09-03 グラクソ グループ リミテッド 核内受容体のリガンド用のアッセイ
EP1140079B1 (fr) * 1998-12-23 2009-06-03 Glaxo Group Limited Methodes de titrage de ligands de recepteurs nucleaires
WO2001020326A2 (fr) * 1999-09-13 2001-03-22 Equitech Laboratories, Inc. Materiaux et procede de detection et de quantification d'un analysat
WO2001040805A1 (fr) * 1999-11-30 2001-06-07 Akzo Nobel N.V. Composes steroidiques destines a des dosages par liaison de recepteur de steroides
WO2001071352A2 (fr) * 2000-03-17 2001-09-27 The Salk Institute For Biological Studies Compositions associees a la formation de complexes et leurs procedes d'utilisation
US7198924B2 (en) 2000-12-11 2007-04-03 Invitrogen Corporation Methods and compositions for synthesis of nucleic acid molecules using multiple recognition sites
US6924311B2 (en) 2001-10-17 2005-08-02 X-Ceptor Therapeutics, Inc. Methods for affecting various diseases utilizing LXR compounds
DE60116109T2 (de) 2001-11-07 2006-09-07 Schering Ag In vitro Screening nach Liganden des Östrogenrezeptors
WO2004010107A2 (fr) * 2002-07-24 2004-01-29 3-Dimensional Pharmaceuticals, Inc. Procede permettant de determiner la regulation de l'elimination des xenobiotiques
WO2004042404A1 (fr) * 2002-11-07 2004-05-21 Erasmus Universiteit Rotterdam Sondes fret et procedes de detection de molecules d'interaction
JP4803976B2 (ja) * 2003-07-09 2011-10-26 独立行政法人科学技術振興機構 細胞内ｉｐ３測定用分子センサー
WO2005021025A2 (fr) * 2003-08-28 2005-03-10 Choongwae Pharma Corporation Modulation de la transcription activee par ?-catenine/tcf
WO2005054438A2 (fr) 2003-12-01 2005-06-16 Invitrogen Corporation Molecule d'acide nucleique contenant des sites de recombinaison et leurs procedes d'utilisation
US20080286260A1 (en) * 2004-03-26 2008-11-20 Bayer Healthcare Ag Diagnostic and Therapeutics for Diseases Associated with Peroxisome Proliferative Activated Receptor Alpha (Ppara)
KR100704011B1 (ko) 2005-02-16 2007-04-04 한국과학기술원 금속나노입자와 양자점의 ｆｒｅｔ에 의한 생체분자특이결합 검출 방법
JP4936476B2 (ja) * 2005-06-28 2012-05-23 第一三共株式会社 Ｌｘｒリガンドの試験方法
JP5264421B2 (ja) 2007-11-22 2013-08-14 富士フイルム株式会社 被験物測定用担体およびその製造方法
WO2009141926A1 (fr) * 2008-05-23 2009-11-26 国立大学法人東京大学 Procédé d'acquisition d'un composé capable d'agir sur le métabolisme du glucose/métabolisme lipidique
WO2015159292A2 (fr) 2014-04-14 2015-10-22 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Procédé et kit permettant de déterminer l'origine tissulaire ou cellulaire de l'adn
JP2019521673A (ja) 2016-06-07 2019-08-08 ザ リージェンツ オブ ザ ユニヴァーシティー オブ カリフォルニア 疾患および状態の分析のためのセルフリーｄｎａメチル化パターン

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997040378A1 (fr) * 1996-04-19 1997-10-30 Vereniging Het Nederlands Kanker Instituut Interaction de la cycline d1 avec le recepteur d'oestrogene et son utilisation dans des dosages
WO1998056806A1 (fr) * 1997-06-12 1998-12-17 The Regents Of The University Of California Proteine de coactivation de facteur de transcription, p/cip
WO1999041608A2 (fr) * 1998-02-12 1999-08-19 Prolifix Limited Interaction de la cycline d1 et des coactivateurs de recepteur steroidien, et utilisations aux fins d'essais

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997040378A1 (fr) * 1996-04-19 1997-10-30 Vereniging Het Nederlands Kanker Instituut Interaction de la cycline d1 avec le recepteur d'oestrogene et son utilisation dans des dosages
WO1998056806A1 (fr) * 1997-06-12 1998-12-17 The Regents Of The University Of California Proteine de coactivation de facteur de transcription, p/cip
WO1999041608A2 (fr) * 1998-02-12 1999-08-19 Prolifix Limited Interaction de la cycline d1 et des coactivateurs de recepteur steroidien, et utilisations aux fins d'essais

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 22 July 1997 (1997-07-22), BELLANGER L ET AL: "Homogeneous time-resolved fluoroimmunoassay for cardiac troponin-I using TRACE technology" XP008042758 Database accession no. PREV199799633726 & CLINICAL CHEMISTRY, vol. 43, no. 6 PART 2, 1997, page S159, 49TH ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CLINICAL CHEMISTRY; ATLANTA, GEORGIA, USA; JULY 20-24, 1997 ISSN: 0009-9147 *
KOLB A J ET AL: "HOMOGENEOUS, TIME-RESOLVED FLUORESCENCE METHOD FOR DRUG DISCOVERY" 1997, HIGH-THROUGHPUT SCREENING, THE DISCOVERY OF BIOACTIVE SUBSTANCES, XX, XX, PAGE(S) 345-360 , XP008042717 * page 354, paragraph 5 - page 355, paragraph 1; figure 12 * *
KOLB J M ET AL: "USE OF A NOVEL HOMOGENEOUS FLUORESCENT TECHNOLOGY IN HIGH THROUGHPUT SCREENING" JOURNAL OF BIOMOLECULAR SCREENING, LARCHMONT, NY, US, vol. 1, no. 4, 1996, pages 203-210, XP008042702 ISSN: 1087-0571 *
LEE S P ET AL: "CHARACTERIZATION OF ENDONUCLEOLYTIC ACTIVITY OF HIV-1 INTEGRASE USING A FLUOROGENIC SUBSTRATE" ANALYTICAL BIOCHEMISTRY, ACADEMIC PRESS, SAN DIEGO, CA, US, vol. 227, 1995, pages 295-301, XP002945389 ISSN: 0003-2697 *
MATHIS G: "PROBING MOLECULAR INTERACTIONS WITH HOMOGENEOUS TECHNIQUES BASED ONRARE EARTH CRYPTATES AND FLUORESCENCE ENERGY TRANSFER" CLINICAL CHEMISTRY, vol. 41, no. 9, 1995, pages 1391-1397, XP001018128 ISSN: 0009-9147 *
ROGERS M V: "LIGHT ON HIGH-THROUGHPUT SCREENING: FLUORESCENCE-BASED ASSAY TECHNOLOGIES" DRUG DISCOVERY TODAY, ELSEVIER SCIENCE LTD, GB, vol. 2, no. 4, April 1997 (1997-04), pages 156-160, XP002916138 ISSN: 1359-6446 *
ROGERS: "Light on high-throughput screening: fluorescence-based assay technologies" DRUG DISCOVERY TODAY, vol. 2, no. 4, April 1997 (1997-04), pages 156-160, XP002916138 *
See also references of WO9918124A1 *
VOEGEL, HEINE, ZECHEL, CHAMBON, GRONEMEYER: "TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors" EMBO JOURNAL, vol. 15, no. 14, 1996, pages 3667-3675, XP002045757 *
ZHOU G ET AL: "Use of homogeneous time-resolved fluorescence energy transfer in the measurement of nuclear receptor activation" METHODS : A COMPANION TO METHODS IN ENZYMOLOGY, ACADEMIC PRESS INC., NEW YORK, NY, US, vol. 25, no. 1, September 2001 (2001-09), pages 54-61, XP002267175 ISSN: 1046-2023 *

Also Published As

Publication number Publication date
EP1021462A4 (fr) 2005-04-13
JP2001519525A (ja) 2001-10-23
WO1999018124A1 (fr) 1999-04-15
CA2305711A1 (fr) 1999-04-15

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