WO1998004686A3 - Enzyme de conversion de preproteines - Google Patents

Enzyme de conversion de preproteines Download PDF

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Publication number
WO1998004686A3
WO1998004686A3 PCT/CA1997/000535 CA9700535W WO9804686A3 WO 1998004686 A3 WO1998004686 A3 WO 1998004686A3 CA 9700535 W CA9700535 W CA 9700535W WO 9804686 A3 WO9804686 A3 WO 9804686A3
Authority
WO
WIPO (PCT)
Prior art keywords
human
silencing
prorenin
renin
adrenal
Prior art date
Application number
PCT/CA1997/000535
Other languages
English (en)
Other versions
WO1998004686A2 (fr
Inventor
Robert Day
Nabil G Seidah
Remi Martel
Michel Chretien
Tim Reudelhuber
Guy Leclerc
Original Assignee
Robert Day
Nabil G Seidah
Remi Martel
Michel Chretien
Tim Reudelhuber
Guy Leclerc
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 CA002203745A external-priority patent/CA2203745A1/fr
Application filed by Robert Day, Nabil G Seidah, Remi Martel, Michel Chretien, Tim Reudelhuber, Guy Leclerc filed Critical Robert Day
Priority to AU36170/97A priority Critical patent/AU3617097A/en
Priority to JP50834398A priority patent/JP2001505870A/ja
Priority to US09/214,555 priority patent/US6380171B1/en
Priority to EP97932685A priority patent/EP0920494A2/fr
Publication of WO1998004686A2 publication Critical patent/WO1998004686A2/fr
Publication of WO1998004686A3 publication Critical patent/WO1998004686A3/fr

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Classifications

    • 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
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6454—Dibasic site splicing serine proteases, e.g. kexin (3.4.21.61); furin (3.4.21.75) and other proprotein convertases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Public Health (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Un clone d'ADNc codant pour la prohormone convertase humaine PC5 a été isolé de l'ARN messager des surrénales humaines. La séquence protéique qui en a été déduite devrait coder pour une préprotéine PC5 de 915 acides aminés, ayant un degré très élevé d'homologie avec ses homologues du rat et de la souris précédemment codées. L'ARNm de la PC5 est détecté dans de multiples tissus humains, notamment le cerveau, les surrénales, la thyroïde, le coeur, le placenta, les poumons et les testicules. Il n'était pas détectable dans le foie et il est présent à des taux inférieurs dans les muscles squelettiques, les reins, le pancréas, l'intestin grêle et l'estomac. La co-transfection des vecteurs d'expression de la PC5 humaine et de la prorénine humaine dans des cellules GH4C1 cultivées provoque la sécrétion de rénine active. L'activation de la prorénine humaine par la PC5, qui dépend d'une paire d'acides aminés basiques aux positions 42 et 43 du prosegment de la prorénine, n'a lieu que dans des cellules contenant des granules sécrétoires à coeur dense. La PC5 humaine a été colocalisée par immunochimie avec la rénine dans la zone glomérulée des surrénales, ce qui suggère qu'elle pourrait participer à l'activation d'un système rénine-angiotensine local dans le cortex surrénal humain. La PC5 est surexprimée dans les coronaires athéroscléreuses. L'atténuation de l'expression de la PC5 par un oligonucléotide antisens spécifique a inhibé efficacement la prolifération des cellules des muscles lisses en culture. En outre, l'antisens a inhibé la sténose de la carotide dans un modèle de lésion de la carotide. Ces résultats indiquent que l'atténuation de la PC5 s'applique à la prévention de la resténose. Les PC pourraient être des cibles de choix pour le traitement de toutes les maladies prolifératives mettant en jeu leur action sur un facteur de croissance donné. Enfin, l'oligonucléotide antisens de la PC5 est à utiliser pour atténuer l'activité de cette enzyme envers la gp160 du VIH, puisqu'ils coexistent dans les lymphocytes T CD4+ et que la glycoprotéine virale peut être clivée par la PC5.
PCT/CA1997/000535 1996-07-26 1997-07-25 Enzyme de conversion de preproteines WO1998004686A2 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
AU36170/97A AU3617097A (en) 1996-07-26 1997-07-25 Pro-protein converting enzyme
JP50834398A JP2001505870A (ja) 1996-07-26 1997-07-25 プロタンパク質変換酵素
US09/214,555 US6380171B1 (en) 1996-07-26 1997-07-25 Pro-protein converting enzyme
EP97932685A EP0920494A2 (fr) 1996-07-26 1997-07-25 Enzyme de conversion de preproteines

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US2100896P 1996-07-26 1996-07-26
US60/021,008 1996-07-26
CA002203745A CA2203745A1 (fr) 1996-07-26 1997-04-25 Enzyme de conversion pro-proteinique
CA2,203,745 1997-04-25

Publications (2)

Publication Number Publication Date
WO1998004686A2 WO1998004686A2 (fr) 1998-02-05
WO1998004686A3 true WO1998004686A3 (fr) 1998-04-23

Family

ID=25679276

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA1997/000535 WO1998004686A2 (fr) 1996-07-26 1997-07-25 Enzyme de conversion de preproteines

Country Status (4)

Country Link
EP (1) EP0920494A2 (fr)
JP (1) JP2001505870A (fr)
AU (1) AU3617097A (fr)
WO (1) WO1998004686A2 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999034823A2 (fr) * 1998-01-09 1999-07-15 University Of Utah Procedes de prevention et de traitement des maladies fibreuses provoquees par l'accumulation excessive d'une matrice extracellulaire induite par le tgf beta a l'aide d'inhibiteurs de la renine
AUPR673001A0 (en) 2001-07-31 2001-08-23 Prince Henry's Institute Of Medical Research Pregnancy-related enzyme activity
AU2003235631A1 (en) * 2002-01-15 2003-07-30 Bayer Aktiengesellschaft Human subtilisin/kexin-like convertase

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994015945A1 (fr) * 1992-12-31 1994-07-21 Texas Biotechnology Corporation Molecules antisens dirigees contre une famille de genes codant un recepteur du facteur de croissance de fibroblastes

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994015945A1 (fr) * 1992-12-31 1994-07-21 Texas Biotechnology Corporation Molecules antisens dirigees contre une famille de genes codant un recepteur du facteur de croissance de fibroblastes

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
DECROLY E ET AL: "THE CONVERTASES FURIN AND PC1 CAN BOTH CLEAVE THE HUMAN IMMUNODEFICIENCY VIRUS (HIV)-1 ENVELOPE GLYCOPROTEIN GP160 INTO GP120 (HIV-I SU) AND GP41 (HIV-I TM)", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 269, no. 16, 22 April 1994 (1994-04-22), pages 12240 - 12247, XP002023318 *
HŸLÈNE C ET AL: "SPECIFIC REGULATION OF GENE EXPRESSION BY ANTISENSE, SENSE AND ANTIGENE NUCLEIC ACIDS", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1049, 1 January 1990 (1990-01-01), pages 99 - 125, XP000570355 *
MERCURE C. ET AL.: "Prohormone convertase PC5 is a candidate processing enzyme for prorenin in the human adrenal cortex", HYPERTENSION, vol. 28, no. 4, October 1996 (1996-10-01), DALLAS, US, pages 840 - 846, XP002046402 *
MIRANDA L. ET AL.: "Isolation of the human PC6 gene encoding the putative host protease for HIV-1 gp160 processing in CD4+ T lymphocytes", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 93, July 1996 (1996-07-01), WASHINGTON US, pages 7695 - 7700, XP002046403 *

Also Published As

Publication number Publication date
JP2001505870A (ja) 2001-05-08
AU3617097A (en) 1998-02-20
EP0920494A2 (fr) 1999-06-09
WO1998004686A2 (fr) 1998-02-05

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