MXPA02009756A - Aislamiento de complejo de proteina de gamma-secretasa funcionalmente activa y metodos de deteccion de la actividad e inhibidores de la misma. - Google Patents

Aislamiento de complejo de proteina de gamma-secretasa funcionalmente activa y metodos de deteccion de la actividad e inhibidores de la misma.

Info

Publication number
MXPA02009756A
MXPA02009756A MXPA02009756A MXPA02009756A MXPA02009756A MX PA02009756 A MXPA02009756 A MX PA02009756A MX PA02009756 A MXPA02009756 A MX PA02009756A MX PA02009756 A MXPA02009756 A MX PA02009756A MX PA02009756 A MXPA02009756 A MX PA02009756A
Authority
MX
Mexico
Prior art keywords
bgr
gamma
app
cleaved
gamma secretase
Prior art date
Application number
MXPA02009756A
Other languages
English (en)
Inventor
David W Smith
Original Assignee
Bristol Myers Squibb Co
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 Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of MXPA02009756A publication Critical patent/MXPA02009756A/es

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Classifications

    • 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
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • C12Q1/37—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
    • 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
    • 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
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701—Details
    • G01N2333/4709—Amyloid plaque core protein
    • 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
    • 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
    • G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Microbiology (AREA)
  • Hematology (AREA)
  • Genetics & Genomics (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Food Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Cell Biology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

La presente invencion proporciona una proteína activa funcionalmente, aislada, que cataliza la segmentacion de un substrato de gamma-secretasa. La actividad funcional de la proteína aislada sugiere que la proteína aislada incluye la gamma-secretasa. En una modalidad, la proteína de gama-secretasa aislada está asociada con PS1. La presente invencion también se refiere a métodos homogéneos para verificar la segmentacion de la proteína precursora °-amiloide (°APP) por la gamma-secretasa, en donde las etapas de aislamiento y recuperacion de los productos de segmentacion han sido eliminadas. La segmentacion puede ser detectada aglutinando un par de aductos fluorescentes al fragmento de °APP gamma-segmentado. Preferentemente, un primer aducto fluorescente se aglutina al extremo carboxi-terminal del fragmento de °APP gama-segmentado, substancialmente sin reactividad cruzada con respecto al °APP no segmentado o con otros tipos de fragmentos de °APP gamma-segmentados, mientras que un segundo aducto fluorescente se aglutina a una porcion dentro de la region mino-terminal sobre el fragmento de °APP gama-segmentado. La deteccion de la aglutinacion al fragmento de °APP gama-segmentado es determinada por la verificacion de la transferencia de la energía fluorescente entre los aductos.
MXPA02009756A 2000-04-03 2001-03-30 Aislamiento de complejo de proteina de gamma-secretasa funcionalmente activa y metodos de deteccion de la actividad e inhibidores de la misma. MXPA02009756A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US19449500P 2000-04-03 2000-04-03
PCT/US2001/010453 WO2001075435A2 (en) 2000-04-03 2001-03-30 Fluorescence assay for gamma-secretase activity and inhibitors

Publications (1)

Publication Number Publication Date
MXPA02009756A true MXPA02009756A (es) 2003-06-17

Family

ID=22717813

Family Applications (1)

Application Number Title Priority Date Filing Date
MXPA02009756A MXPA02009756A (es) 2000-04-03 2001-03-30 Aislamiento de complejo de proteina de gamma-secretasa funcionalmente activa y metodos de deteccion de la actividad e inhibidores de la misma.

Country Status (8)

Country Link
US (2) US6713248B2 (es)
EP (1) EP1305634A2 (es)
JP (1) JP2004505608A (es)
AU (2) AU2001249717B2 (es)
CA (1) CA2405332A1 (es)
IL (1) IL151828A0 (es)
MX (1) MXPA02009756A (es)
WO (1) WO2001075435A2 (es)

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WO2003057165A2 (en) 2002-01-04 2003-07-17 The Rockefeller University COMPOSITIONS AND METHODS FOR PREVENTION AND TREATMENT OF AMYLOID-β PEPTIDE-RELATED DISORDERS
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Also Published As

Publication number Publication date
CA2405332A1 (en) 2001-10-11
AU4971701A (en) 2001-10-15
IL151828A0 (en) 2003-04-10
US20040121411A1 (en) 2004-06-24
WO2001075435A2 (en) 2001-10-11
AU2001249717B2 (en) 2006-03-30
WO2001075435A3 (en) 2002-08-08
JP2004505608A (ja) 2004-02-26
US6713248B2 (en) 2004-03-30
US20020025540A1 (en) 2002-02-28
EP1305634A2 (en) 2003-05-02

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