ES2132644T3 - Metodo para reproducir in vitro la actividad proteolitica de la proteasa ns3 del virus de la hepatitis c (vhc). - Google Patents

Metodo para reproducir in vitro la actividad proteolitica de la proteasa ns3 del virus de la hepatitis c (vhc).

Info

Publication number
ES2132644T3
ES2132644T3 ES95909937T ES95909937T ES2132644T3 ES 2132644 T3 ES2132644 T3 ES 2132644T3 ES 95909937 T ES95909937 T ES 95909937T ES 95909937 T ES95909937 T ES 95909937T ES 2132644 T3 ES2132644 T3 ES 2132644T3
Authority
ES
Spain
Prior art keywords
ns4a
hcv
precursor
vitro
activity
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.)
Expired - Lifetime
Application number
ES95909937T
Other languages
English (en)
Inventor
Francesco Raffaele De
Cristina Failla
Licia Tomei
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.)
Istituto di Ricerche di Biologia Molecolare P Angeletti SpA
Original Assignee
Istituto di Ricerche di Biologia Molecolare P Angeletti SpA
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 Istituto di Ricerche di Biologia Molecolare P Angeletti SpA filed Critical Istituto di Ricerche di Biologia Molecolare P Angeletti SpA
Application granted granted Critical
Publication of ES2132644T3 publication Critical patent/ES2132644T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime 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
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
    • 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
    • G01N33/576—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis
    • G01N33/5767—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis non-A, non-B hepatitis
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/24011—Flaviviridae
    • C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
    • C12N2770/24222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

ESTE ES UN METODO PARA REPRODUCIR IN VITRO LA ACTIVIDAD DE PROTEASA DE SERINA ASOCIADA CON LA PROTEINA NS3 DEL VHC. EL METODO INCLUYE EL USO TANTO DE LAS SECUENCIAS CONTENIDAS EN LA NS3 COMO LAS CONTENIDAS EN LA NS4A. ESTE METODO APROVECHA LA CAPACIDAD DE LA PROTEINA NS4A DEL VHC O DE LAS SECUENCIAS QUE CONTIENE PARA ACTUAR COMO UN COFACTOR DE LA ACTIVIDAD DE LA PROTEASA DE SERINA O, DE FORMA MAS GENERAL, DE LAS ACTIVIDADES ENZIMATICAS ASOCIADAS CON NS3. LA ACTIVIDAD OPTIMA DE PROTEASA DE SERINA SE OBTIENE CUANDO NS4A ESTA PRESENTE EN UN RADIO MOLAR DE AL MENOS 1:1, CON NS3. NS3 Y NS4A TAMBIEN PUEDEN INCORPORARSE EN LA MEZCLA DE REACCION EN FORMA DEL PRECURSOR NS3-NS4A, YA QUE ESTE PRECURSOR GENERARA, A TRAVES DE UN MECANISMO AUTOPROTEOLITICO, CANTIDADES EQUIMOLARES DE NS3 Y NS4A. TAMBIEN ES POSIBLE MUTAR EL SITIO DE RUPTURA ENTRE NS3 Y NS4A EN UN PRECURSOR PARA QUE NS4A SE MANTENGA UNIDA COVALENTEMENTE A NS3. LAS SECUENCIAS QUE NO TIENEN INFLUENCIA SOBRE LA ACTIVIDAD PROTEOLITICA DE NS3 PUEDEN ELIMINARSE A CONTINUACION DE DICHO PRECURSOR NO PROTEOLIZABLE. ESTA INVENCION TAMBIEN SE RELACIONA CON UNA COMPOSICION DE MATERIA QUE INCLUYE LAS SECUENCIAS CONTENIDAS EN NS3 Y NS4A Y CON EL USO DE ESTAS COMPOSICIONES PARA ESTABLECER UNA PRUEBA ENZIMATICA CAPAZ DE SELECCIONAR, CON FINES TERAPEUTICOS, COMPUESTOS QUE INHIBAN LA ACTIVIDAD ENZIMATICA ASOCIADA CON NS3. LA FIGURA MUESTRA LOS PLASMIDOS VECTORES UTILIZADOS EN EL METODO PARA ACTIVAR A LA PROTEASA DE NS3 DEL VHC EN CELULAS CULTIVADAS E IN VITRO.
ES95909937T 1994-02-23 1995-02-14 Metodo para reproducir in vitro la actividad proteolitica de la proteasa ns3 del virus de la hepatitis c (vhc). Expired - Lifetime ES2132644T3 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ITRM940092A IT1272179B (it) 1994-02-23 1994-02-23 Metodologia per riprodurre in vitro l'attivita' proteolitica della proteasi ns3 del virus hcv.

Publications (1)

Publication Number Publication Date
ES2132644T3 true ES2132644T3 (es) 1999-08-16

Family

ID=11402272

Family Applications (1)

Application Number Title Priority Date Filing Date
ES95909937T Expired - Lifetime ES2132644T3 (es) 1994-02-23 1995-02-14 Metodo para reproducir in vitro la actividad proteolitica de la proteasa ns3 del virus de la hepatitis c (vhc).

Country Status (15)

Country Link
US (1) US5739002A (es)
EP (1) EP0746333B1 (es)
JP (1) JP3280384B2 (es)
AT (1) ATE179611T1 (es)
AU (1) AU691259B2 (es)
BR (1) BR9506931A (es)
CA (1) CA2182521C (es)
DE (1) DE69509504T2 (es)
DK (1) DK0746333T3 (es)
ES (1) ES2132644T3 (es)
GR (1) GR3030166T3 (es)
HK (1) HK1010988A1 (es)
IT (1) IT1272179B (es)
RU (1) RU2149185C1 (es)
WO (1) WO1995022985A1 (es)

Families Citing this family (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5767233A (en) * 1995-05-12 1998-06-16 Schering Corporation Soluble cleavable substrates of the hepatitis C virus protease
US5843752A (en) * 1995-05-12 1998-12-01 Schering Corporation Soluble active hepatitis C virus protease
IT1278077B1 (it) * 1995-05-25 1997-11-17 Angeletti P Ist Richerche Bio Metodologia per riprodurre in vitro le attivita' di rna polimerasi rna-dipendente e di nucleotidiltransferasi terminale codificate dal
JPH11513890A (ja) * 1996-05-10 1999-11-30 シェーリング コーポレイション Ｃ型肝炎ウイルスｎｓ３プロテアーゼの合成インヒビター
US5990276A (en) * 1996-05-10 1999-11-23 Schering Corporation Synthetic inhibitors of hepatitis C virus NS3 protease
EP1364961B1 (en) * 1996-09-12 2006-11-22 Vertex Pharmaceuticals Incorporated Crystallizable compositions comprising a hepatitis c virus ns3 protease domain/ns4a complex and crystals thereby obtained
US6153579A (en) * 1996-09-12 2000-11-28 Vertex Pharmaceuticals, Incorporated Crystallizable compositions comprising a hepatitis C virus NS3 protease domain/NS4A complex
US5861297A (en) * 1996-09-27 1999-01-19 Merck & Co., Inc. Detergent-free hepatitis C protease
AU4904397A (en) * 1996-10-17 1998-05-11 Chiron Corporation Protease regulator screening assay
WO1998037180A2 (en) * 1997-02-22 1998-08-27 Abbott Laboratories Hcv fusion protease and polynucleotide encoding same
US6251583B1 (en) 1998-04-27 2001-06-26 Schering Corporation Peptide substrates for HCV NS3 protease assays
US6280940B1 (en) 1998-08-05 2001-08-28 Agouron Pharmaceuticals, Inc. Reporter gene system for use in cell-based assessment of inhibitors of the Hepatitis C virus protease
US6323180B1 (en) 1998-08-10 2001-11-27 Boehringer Ingelheim (Canada) Ltd Hepatitis C inhibitor tri-peptides
WO2000040707A1 (en) * 1999-01-08 2000-07-13 Bristol-Myers Squibb Co. Modified forms of hepatitis c virus ns3 protease
CA2376965A1 (en) * 1999-07-07 2001-01-11 Timothy Patrick Forsyth Peptide boronic acid inhibitors of hepatitis c virus protease
WO2001038538A1 (en) * 1999-11-23 2001-05-31 Viropharma Incorporated Polymerase compositions and methods of use thereof
MY164523A (en) 2000-05-23 2017-12-29 Univ Degli Studi Cagliari Methods and compositions for treating hepatitis c virus
US7244721B2 (en) * 2000-07-21 2007-07-17 Schering Corporation Peptides as NS3-serine protease inhibitors of hepatitis C virus
ATE461207T1 (de) * 2000-07-21 2010-04-15 Schering Corp Peptide als inhibitoren der ns3-serinprotease des hepatitis c virus
AR029851A1 (es) * 2000-07-21 2003-07-16 Dendreon Corp Nuevos peptidos como inhibidores de ns3-serina proteasa del virus de hepatitis c
WO2002008187A1 (en) * 2000-07-21 2002-01-31 Schering Corporation Novel peptides as ns3-serine protease inhibitors of hepatitis c virus
US7022830B2 (en) 2000-08-17 2006-04-04 Tripep Ab Hepatitis C virus codon optimized non-structural NS3/4A fusion gene
EP1423522A2 (en) * 2001-01-23 2004-06-02 Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. Hepatitis c virus replicons and replicon enhanced cells
WO2003026589A2 (en) * 2001-09-28 2003-04-03 Idenix (Cayman) Limited Methods and compositions for treating hepatitis c virus using 4'-modified nucleosides
ATE467680T1 (de) 2001-10-11 2010-05-15 Merck Sharp & Dohme Hepatitis-c-virus-impfstoff
DE60236364D1 (en) 2001-10-11 2010-06-24 Angeletti P Ist Richerche Bio Hepatitis-c-virus-impfstoff
DE60326831D1 (en) 2002-04-16 2009-05-07 Merck & Co Inc Hepatitis-c-virus-testsysteme
CA2514918C (en) * 2003-02-13 2012-07-03 Merck & Co., Inc. Method to confer cell culture replication activity to different hepatitis c virus isolates
US7414031B2 (en) * 2004-11-22 2008-08-19 Genelabs Technologies, Inc. 5-nitro-nucleoside compounds for treating viral infections
WO2006093986A1 (en) * 2005-02-28 2006-09-08 Genelabs Technologies, Inc. Tricyclic-nucleoside prodrugs for treating viral infections
US7834145B2 (en) * 2005-03-22 2010-11-16 Merck Sharp & Dohme Corp. HCV protease substrates
AR056327A1 (es) * 2005-04-25 2007-10-03 Genelabs Tech Inc Compuestos de nucleosidos para el tratamiento de infecciones virales
BRPI0612124A2 (pt) * 2005-06-24 2010-10-19 Genelabs Tech Inc derivados de heteroarila para o tratamento de viroses
CA2627247C (en) * 2005-10-28 2013-04-02 Boehringer Ingelheim International Gmbh Hepatitis c virus ns2/3 activity assay
WO2007145894A2 (en) 2006-06-08 2007-12-21 Merck & Co., Inc. A rapid method to determine inhibitor sensitivity of ns3/4a protease sequences
RU2009105837A (ru) * 2006-07-20 2010-08-27 СмитКлайн Бичем Копэрейшн (US) Полициклические противовирусные соединения (варианты), фармацевтическая композиция на их основе, способ лечения вирусной инфекции с ее помощью и названные соединения для изготовления лекарственных средств
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EP2595983A1 (en) 2010-07-22 2013-05-29 Novartis AG 2,3,5-trisubstituted thiophene compounds and uses thereof
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US11965191B2 (en) 2018-01-18 2024-04-23 California Institute Of Technology Programmable protein circuits in living cells
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Also Published As

Publication number Publication date
ATE179611T1 (de) 1999-05-15
ITRM940092A0 (it) 1994-02-23
IT1272179B (it) 1997-06-16
JP3280384B2 (ja) 2002-05-13
AU1822395A (en) 1995-09-11
DE69509504D1 (de) 1999-06-10
US5739002A (en) 1998-04-14
WO1995022985A1 (en) 1995-08-31
HK1010988A1 (en) 1999-07-02
GR3030166T3 (en) 1999-08-31
EP0746333B1 (en) 1999-05-06
DK0746333T3 (da) 1999-11-01
BR9506931A (pt) 1997-09-09
AU691259B2 (en) 1998-05-14
RU2149185C1 (ru) 2000-05-20
ITRM940092A1 (it) 1995-08-23
DE69509504T2 (de) 1999-09-02
EP0746333A1 (en) 1996-12-11
CA2182521C (en) 1999-07-06
JPH10500005A (ja) 1998-01-06
CA2182521A1 (en) 1995-08-31

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