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WO1999066065A3 - Proteasomal activity - Google Patents

Proteasomal activity Download PDF

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Publication number
WO1999066065A3
WO1999066065A3 PCT/GB1999/001840 GB9901840W WO9966065A3 WO 1999066065 A3 WO1999066065 A3 WO 1999066065A3 GB 9901840 W GB9901840 W GB 9901840W WO 9966065 A3 WO9966065 A3 WO 9966065A3
Authority
WO
WIPO (PCT)
Prior art keywords
compounds
assays
identifying
proteasomal
methods
Prior art date
Application number
PCT/GB1999/001840
Other languages
French (fr)
Other versions
WO1999066065A2 (en
Inventor
Hans-Peter Schmid
Franck Petit
Peter-Michael Kloetzel
Anne-Sophie Jarrousse
Karine Gautier
Saloua Badaoui
Said Mouzeyar
Paul Nicolas
Original Assignee
Bridgehead Technologies Limite
Schmid Hans Peter
Franck Petit
Kloetzel Peter Michael
Jarrousse Anne Sophie
Karine Gautier
Saloua Badaoui
Said Mouzeyar
Paul Nicolas
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
Priority claimed from GBGB9812756.6A external-priority patent/GB9812756D0/en
Priority claimed from GBGB9812759.0A external-priority patent/GB9812759D0/en
Priority claimed from GBGB9812758.2A external-priority patent/GB9812758D0/en
Priority claimed from GBGB9812760.8A external-priority patent/GB9812760D0/en
Priority claimed from GBGB9812757.4A external-priority patent/GB9812757D0/en
Application filed by Bridgehead Technologies Limite, Schmid Hans Peter, Franck Petit, Kloetzel Peter Michael, Jarrousse Anne Sophie, Karine Gautier, Saloua Badaoui, Said Mouzeyar, Paul Nicolas filed Critical Bridgehead Technologies Limite
Priority to JP2000554874A priority Critical patent/JP2002518020A/en
Priority to CA002330210A priority patent/CA2330210A1/en
Priority to EP99957075A priority patent/EP1088100A2/en
Priority to AU42811/99A priority patent/AU4281199A/en
Publication of WO1999066065A2 publication Critical patent/WO1999066065A2/en
Publication of WO1999066065A3 publication Critical patent/WO1999066065A3/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/34Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • C12Q1/37Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • A61P31/18Antivirals for RNA viruses for HIV
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q2337/00N-linked chromogens for determinations of peptidases and proteinases
    • C12Q2337/20Coumarin derivatives
    • C12Q2337/227-Amino-4-methylcoumarin, i.e. AMC, MCA
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/01DNA viruses
    • G01N2333/02Hepadnaviridae, e.g. hepatitis B virus
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/08RNA viruses
    • G01N2333/15Retroviridae, e.g. bovine leukaemia virus, feline leukaemia virus, feline leukaemia virus, human T-cell leukaemia-lymphoma virus
    • G01N2333/155Lentiviridae, e.g. visna-maedi virus, equine infectious virus, FIV, SIV
    • G01N2333/16HIV-1, HIV-2
    • G01N2333/163Regulatory proteins, e.g. tat, nef, rev, vif, vpu, vpr, vpt, vpx
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00Screening for compounds of potential therapeutic value
    • G01N2500/02Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • Virology (AREA)
  • Genetics & Genomics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • AIDS & HIV (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Rheumatology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biophysics (AREA)
  • Pain & Pain Management (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

The present invention relates to modulation and/or regulation of proteasomal activity. The invention provides assay methods for identifying compounds which inhibit viral replication and pathogenesis, for identifying inhibitors of the nuclease-inhibitory function of the human immunodeficiency virus TAT protein, for identifying inhibitors of the protease-inhibitory function of the human immunodeficiency virus TAT protein, for identifying compounds which change the concentrations of regulatory proteins by modulating the rate of proteasomal destruction of specific mRNAs, and methods for generating resistance to bacterial or viral infection damage. The invention provides assays, kits for carrying out said assays, compounds identified by said assays, together with amino acid sequences encoding said compounds and medicinal compositions derived therefrom. Where legally permissible the invention also provides methods of treatment based on the modulation/regulation of proteasomal activity.
PCT/GB1999/001840 1998-06-13 1999-06-10 Proteasomal activity WO1999066065A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2000554874A JP2002518020A (en) 1998-06-13 1999-06-10 Proteasome activity
CA002330210A CA2330210A1 (en) 1998-06-13 1999-06-10 Proteasomal activity
EP99957075A EP1088100A2 (en) 1998-06-13 1999-06-10 Proteasomal activity
AU42811/99A AU4281199A (en) 1998-06-13 1999-06-10 Proteasomal activity

Applications Claiming Priority (10)

Application Number Priority Date Filing Date Title
GB9812758.2 1998-06-13
GB9812757.4 1998-06-13
GBGB9812756.6A GB9812756D0 (en) 1998-06-13 1998-06-13 Assay procedure for identifying inhibitors of the nuclease-inhibitory function of the human immunodeficiency virus tat protein
GBGB9812759.0A GB9812759D0 (en) 1998-06-13 1998-06-13 A procedure for generating resistance to bacterial or viral infection damage
GBGB9812758.2A GB9812758D0 (en) 1998-06-13 1998-06-13 Proteasomal destruction of mRNA
GB9812756.6 1998-06-13
GBGB9812760.8A GB9812760D0 (en) 1998-06-13 1998-06-13 A method for identifying compounds which inhibit viral replication and pathogenesis
GB9812759.0 1998-06-13
GBGB9812757.4A GB9812757D0 (en) 1998-06-13 1998-06-13 Assay procedure for identifying inhibitors of the protease-inhibitory function of the human immunodeficiency virus tat protein
GB9812760.8 1998-06-13

Publications (2)

Publication Number Publication Date
WO1999066065A2 WO1999066065A2 (en) 1999-12-23
WO1999066065A3 true WO1999066065A3 (en) 2000-04-20

Family

ID=27517463

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1999/001840 WO1999066065A2 (en) 1998-06-13 1999-06-10 Proteasomal activity

Country Status (5)

Country Link
EP (1) EP1088100A2 (en)
JP (1) JP2002518020A (en)
AU (1) AU4281199A (en)
CA (1) CA2330210A1 (en)
WO (1) WO1999066065A2 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR9914648A (en) * 1998-10-20 2001-11-27 Millennium Pharm Inc Process to monitor drug action of proteasome inhibitor

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995029244A1 (en) * 1994-04-26 1995-11-02 Wisconsin Alumni Research Foundation Method to increase regulatory molecule production
WO1997025618A1 (en) * 1996-01-05 1997-07-17 Icos Corporation Cytoplasmic modulators of integrin binding/signalling
WO1998036070A1 (en) * 1997-02-18 1998-08-20 Signal Pharmaceuticals, Inc. COMPOSITIONS AND METHODS FOR MODULATING CELLULAR NF-λB ACTIVATION
EP0943624A1 (en) * 1998-03-12 1999-09-22 Universiteit Utrecht Peptidic inhibitors of down-regulation of growth hormone receptor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995029244A1 (en) * 1994-04-26 1995-11-02 Wisconsin Alumni Research Foundation Method to increase regulatory molecule production
WO1997025618A1 (en) * 1996-01-05 1997-07-17 Icos Corporation Cytoplasmic modulators of integrin binding/signalling
WO1998036070A1 (en) * 1997-02-18 1998-08-20 Signal Pharmaceuticals, Inc. COMPOSITIONS AND METHODS FOR MODULATING CELLULAR NF-λB ACTIVATION
EP0943624A1 (en) * 1998-03-12 1999-09-22 Universiteit Utrecht Peptidic inhibitors of down-regulation of growth hormone receptor

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
ADAMS J ET AL: "CHAPTER 28. NOVEL INHIBITORS OF THE PROTEASOME AND THEIR THERAPEUTIC USE IN INFLAMMATION", ANNUAL REPORTS IN MEDICINAL CHEMISTRY,US,SAN DIEGO, pages 279-288, XP000791150, ISSN: 0065-7743 *
DATABASE SWISSPROT 1 August 1992 (1992-08-01), DEMARTINO, G.N. ET AL.: "Multicatalytic endopeptidase complex zeta chain." *
DEMARTINO, G.N.: "The primary structures of four subunits of the human, high molecular weight proteinase, macropain (proteasome), are distinct but homologous.", BIOCHEM. BIOPHYS. ACTA, vol. 1079, 1991, pages 29 - 38, XP000865674 *
LEVITSKAYA, J. ET AL.: "Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein-Barr virus nuclear Antigen", PROCEEDINGS OF THE NATIONAL ACADAMY OF SCIENCES USA, vol. 94, November 1997 (1997-11-01), pages 12616 - 12621, XP002126609 *
PETIT, F. ET AL.: "Involvement of proteasomal suunits zeta en iota in RNA degradation", BIOCHEM. J., vol. 326, 1997, pages 93 - 98, XP000865614 *
PETIT, F. ET AL.: "Proteasome (prosome) associated endonuclease activity", MOLECULAR BIOLOGY REPORTS, vol. 24, no. 1-2, March 1997 (1997-03-01), pages 113 - 117, XP002126606 *
POUCH, M-N. ET AL.: "Identification and initial characterisation of a specific proteasome(prosome) associated RNase activity", THE JOURNAL FO BIOLOGICAL CHEMISTRY, vol. 270, no. 37, 1995, pages 22023 - 22028, XP002126608 *
SCHUBERT, U. ET AL.: "CD4 glycoprotein degradation induced by human immunodeficiency virus type 1 Vpu protein requires the function of proteasomes and the ubiquitin-conjugation pathway", JOURNAL OF VIROLOGY, vol. 72, no. 3, March 1998 (1998-03-01), pages 2280 - 2288, XP002121469 *
SCHWARTZ, O. ET AL.: "Antiviral activity of the proteasome on incoming human immunodeficiency virus type 1", JOURNAL OF VIROLOGY, vol. 72, no. 5, May 1998 (1998-05-01), pages 3845 - 3850, XP002121467 *

Also Published As

Publication number Publication date
WO1999066065A2 (en) 1999-12-23
AU4281199A (en) 2000-01-05
CA2330210A1 (en) 1999-12-23
EP1088100A2 (en) 2001-04-04
JP2002518020A (en) 2002-06-25

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