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WO1998003538A3 - Toxines a regulation par signaux et mediation par clivage - Google Patents

Toxines a regulation par signaux et mediation par clivage Download PDF

Info

Publication number
WO1998003538A3
WO1998003538A3 PCT/US1997/010941 US9710941W WO9803538A3 WO 1998003538 A3 WO1998003538 A3 WO 1998003538A3 US 9710941 W US9710941 W US 9710941W WO 9803538 A3 WO9803538 A3 WO 9803538A3
Authority
WO
WIPO (PCT)
Prior art keywords
domain
sitoxin
cleavage
effector domain
target cell
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.)
Ceased
Application number
PCT/US1997/010941
Other languages
English (en)
Other versions
WO1998003538A2 (fr
Inventor
Alexander Varshavsky
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.)
California Institute of Technology
Original Assignee
California Institute of Technology
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 California Institute of Technology filed Critical California Institute of Technology
Publication of WO1998003538A2 publication Critical patent/WO1998003538A2/fr
Publication of WO1998003538A3 publication Critical patent/WO1998003538A3/fr
Anticipated expiration legal-status Critical
Ceased 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
    • C07K14/415—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/55—Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/95—Fusion polypeptide containing a motif/fusion for degradation (ubiquitin fusions, PEST sequence)

Landscapes

  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Wood Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Physics & Mathematics (AREA)
  • Botany (AREA)
  • Plant Pathology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne une nouvelle classe de molécules dénommées sitoxines (toxines à régulation par signaux et médiation par clivage). Une sitoxine associe plusieurs domaines fonctionnels de façon à produire une molécule active sur le plan thérapeutique. Plus spécifiquement, une sitoxine est constituée d'un domaine effecteur; d'un domaine portant un fragment de signalisation intracellulaire; et d'un domaine situé entre le domaine effecteur et le domaine portant le fragment de signalisation intracellulaire, qui spécifie un site de clivage pour une protéase prédéterminée. L'invention concerne également des méthodes permettant de tuer sélectivement une cellule cible dont on sait qu'elle contient une protéase prédéterminée. Ces méthodes font appel à l'introduction d'une sitoxine dans la cellule cible. La sitoxine peut être introduite soit directement, soit par l'intermédiaire d'un vecteur d'expression. Après introduction de la sitoxine dans la cellule cible, le clivage par la protéase prédéterminée sépare le domaine effecteur de la sitoxine du fragment de signalisation intracellulaire. Le domaine effecteur, une fois séparé, a une vie plus longue (il est donc plus toxique), ou bien il passe d'un compartiment cellulaire où il n'est pas toxique à un compartiment cellulaire où il est capable d'exercer son effet.
PCT/US1997/010941 1995-10-27 1997-10-24 Toxines a regulation par signaux et mediation par clivage Ceased WO1998003538A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US54927595A 1995-10-27 1995-10-27
US08/549,275 1995-10-27

Publications (2)

Publication Number Publication Date
WO1998003538A2 WO1998003538A2 (fr) 1998-01-29
WO1998003538A3 true WO1998003538A3 (fr) 1998-03-26

Family

ID=24192333

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/010941 Ceased WO1998003538A2 (fr) 1995-10-27 1997-10-24 Toxines a regulation par signaux et mediation par clivage

Country Status (2)

Country Link
CA (1) CA2236036A1 (fr)
WO (1) WO1998003538A2 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69926647T2 (de) * 1998-10-16 2006-11-09 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Durch molekulares pathogenicid vermittelte krankheitsresistenz in pflanzen
WO2000050089A2 (fr) * 1999-02-26 2000-08-31 Mindset Biopharmaceuticals (Usa) Ltd. Regulation de la stabilite de proteines de recombinaison, anticorps et produits convenant pour cette regulation
WO2012139112A1 (fr) * 2011-04-08 2012-10-11 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Fusions d'ubiquitine pour améliorer l'efficacité de toxines ciblées à action cytosolique

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BIOCONJUGATE CHEM., 1993, Vol. 4, COOK J.P. et al., "Biologically Active Interleukin 2-Ricin A Chain Fusion Proteins May Require Intracellular Proteolytic Cleavage to Exhibit a Cytotoxic Effect", pages 440-447. *
EUR. J. BIOCHEM., 1991, Vol. 199, LOUIS J.M. et al., "Autoprocessing of the HIV-1 Protease Using Purified Wild-Type and Mutated Fusion Proteins Expressed at High Levels in Escherichia Coli", pages 361-369. *

Also Published As

Publication number Publication date
CA2236036A1 (fr) 1998-01-29
WO1998003538A2 (fr) 1998-01-29

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