IT1272179B - Metodologia per riprodurre in vitro l'attivita' proteolitica della proteasi ns3 del virus hcv. - Google Patents

Metodologia per riprodurre in vitro l'attivita' proteolitica della proteasi ns3 del virus hcv.

Info

Publication number
IT1272179B
IT1272179B ITRM940092A ITRM940092A IT1272179B IT 1272179 B IT1272179 B IT 1272179B IT RM940092 A ITRM940092 A IT RM940092A IT RM940092 A ITRM940092 A IT RM940092A IT 1272179 B IT1272179 B IT 1272179B
Authority
IT
Italy
Prior art keywords
ns4a
methodology
precursor
protease
hcv
Prior art date
Application number
ITRM940092A
Other languages
English (en)
Inventor
Francesco Raffaele De
Cristina Failla
Licia Tomei
Original Assignee
Angeletti P Ist Richerche Bio
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 Angeletti P Ist Richerche Bio filed Critical Angeletti P Ist Richerche Bio
Publication of ITRM940092A0 publication Critical patent/ITRM940092A0/it
Priority to ITRM940092A priority Critical patent/IT1272179B/it
Priority to DK95909937T priority patent/DK0746333T3/da
Priority to PCT/IT1995/000018 priority patent/WO1995022985A1/en
Priority to DE69509504T priority patent/DE69509504T2/de
Priority to BR9506931A priority patent/BR9506931A/pt
Priority to CA002182521A priority patent/CA2182521C/en
Priority to US08/700,356 priority patent/US5739002A/en
Priority to AU18223/95A priority patent/AU691259B2/en
Priority to AT95909937T priority patent/ATE179611T1/de
Priority to RU96119350A priority patent/RU2149185C1/ru
Priority to EP95909937A priority patent/EP0746333B1/en
Priority to JP52223995A priority patent/JP3280384B2/ja
Priority to ES95909937T priority patent/ES2132644T3/es
Publication of ITRM940092A1 publication Critical patent/ITRM940092A1/it
Application granted granted Critical
Publication of IT1272179B publication Critical patent/IT1272179B/it
Priority to HK98111982A priority patent/HK1010988A1/xx
Priority to GR990401236T priority patent/GR3030166T3/el

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

Abstract

Si tratta di una metodologia, per riprodurre in vitro l'attività di serino - proteasi associata alla proteina NS3 di HCV, che comprende l'utilizzo sia di sequenze contenute in NS3 che di sequenze contenute in NS4A. Questa metodologia sfrutta la capacità della proteina di HCV NS4A, o di sequenze in essa contenute, di agire come cofattore della attività serino - proteasica o più in generale di attività enzimatiche associate a NS3. L'attività ottimale di serino - proteasi si ottiene quando NS4A è presente in un rapporto molare di almeno 1:1 con NS3. NS3 ed NS4A possono essere anche incorporati nella miscela di reazione come precursore NS3-NS4A, in quanto questo precursore genererà, mediante un evento autoproteolitico, quantità equimolari di NS3 ed NS4A. E' anche possibile mutare il sito di taglio tra NS3 ed NS4A in un precursore, in modo che NS4A rimanga covalentemente legato a NS3. Da tale precursore non proteolizzabile possono essere successivamente rimosse le sequenze che non influenzano l'attività proteolitica di NS3.L'invenzione si riferisce anche ad una composizione di materia che comprende sequenze contenute in NS3 ed NS4A, e all'uso di queste composizioni per la messa a punto di un saggio enzimatico capace di selezionare, a fini terapeutici, composti inibitori dell'attività enzimatica associata a NS3.La figura rappresenta vettori plasmidici utilizzati nella metodologia per l'attivazione della proteasi NS3 di HCV in cellule in coltura e in vitro.
ITRM940092A 1994-02-23 1994-02-23 Metodologia per riprodurre in vitro l'attivita' proteolitica della proteasi ns3 del virus hcv. IT1272179B (it)

Priority Applications (15)

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.
AT95909937T ATE179611T1 (de) 1994-02-23 1995-02-14 Verfahrenm zum in vitro herstellung der proteolytischen wirkung von ns3 hepatitis c virus (hcv)
EP95909937A EP0746333B1 (en) 1994-02-23 1995-02-14 Method for reproducing in vitro the proteolytic activity of the ns3 protease of hepatitis c virus (hcv)
DE69509504T DE69509504T2 (de) 1994-02-23 1995-02-14 Verfahrenm zum in vitro herstellung der proteolytischen wirkung von ns3 hepatitis c virus (hcv)
BR9506931A BR9506931A (pt) 1994-02-23 1995-02-14 Processo para reproduzir in vitro a atividade proteolítica da protease ns3 de hcv composiçao de matéria e uso da mesma
CA002182521A CA2182521C (en) 1994-02-23 1995-02-14 Method for reproducing in vitro the proteolytic activity of the ns3 protease of hepatitis c virus (hcv)
US08/700,356 US5739002A (en) 1994-02-23 1995-02-14 Method for reproducing in vitro the Proteolytic activity of the NS3 protease of hepatitis C virus (HCV)
AU18223/95A AU691259B2 (en) 1994-02-23 1995-02-14 Method for reproducing in vitro the proteolytic activity of the NS3 protease of hepatitis C virus (HCV)
DK95909937T DK0746333T3 (da) 1994-02-23 1995-02-14 Fremgangsmåde til in vitro reproduktion af den proteolytiske aktivitet af hepatitis C virus (HCV) NS3 proteasen
RU96119350A RU2149185C1 (ru) 1994-02-23 1995-02-14 Способ репродукции in vitro протеолитической активности ns3 протеазы вируса гепатита c (нсу)
PCT/IT1995/000018 WO1995022985A1 (en) 1994-02-23 1995-02-14 Method for reproducing in vitro the proteolytic activity of the ns3 protease of hepatitis c virus (hcv)
JP52223995A JP3280384B2 (ja) 1994-02-23 1995-02-14 Ｃ型肝炎ウイルス（ｈｃｖ）のｎｓ３プロテアーゼの蛋白分解活性のインビトロにおける再生方法
ES95909937T 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).
HK98111982A HK1010988A1 (en) 1994-02-23 1998-11-13 Method for reproducing in vitro the proteolytic activity of the ns3 protease of hepatitis c virus (hcv)
GR990401236T GR3030166T3 (en) 1994-02-23 1999-05-07 Method for reproducing in vitro the proteolytic activity of the ns3 protease of hepatitis c virus (hcv)

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 (3)

Publication Number Publication Date
ITRM940092A0 ITRM940092A0 (it) 1994-02-23
ITRM940092A1 ITRM940092A1 (it) 1995-08-23
IT1272179B true IT1272179B (it) 1997-06-16

Family

ID=11402272

Family Applications (1)

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

Country Status (15)

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

Families Citing this family (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5843752A (en) * 1995-05-12 1998-12-01 Schering Corporation Soluble active hepatitis C virus protease
US5767233A (en) * 1995-05-12 1998-06-16 Schering Corporation Soluble cleavable substrates of the 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
AU2933797A (en) * 1996-05-10 1997-12-05 Schering Corporation Synthetic inhibitors of hepatitis c virus ns3 protease
US5990276A (en) * 1996-05-10 1999-11-23 Schering Corporation Synthetic inhibitors of hepatitis C virus NS3 protease
US6153579A (en) * 1996-09-12 2000-11-28 Vertex Pharmaceuticals, Incorporated Crystallizable compositions comprising a hepatitis C virus NS3 protease domain/NS4A complex
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
US5861297A (en) * 1996-09-27 1999-01-19 Merck & Co., Inc. Detergent-free hepatitis C protease
WO1998016657A1 (en) * 1996-10-17 1998-04-23 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
EP1196436A2 (en) * 1999-07-07 2002-04-17 Bristol-Myers Squibb Pharma Company Peptide boronic acid inhibitors of hepatitis c virus protease
EP1257650A4 (en) * 1999-11-23 2004-03-24 Viropharma Inc POLYMERASE COMPOSITIONS AND METHODS FOR THEIR USE
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
MXPA03000626A (es) * 2000-07-21 2004-07-30 Schering Corp Nuevos peptidos como inhibidores de ns3-serina proteasa del virus de la hepatitis c.
DE60141608D1 (de) * 2000-07-21 2010-04-29 Dendreon 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
US7022830B2 (en) 2000-08-17 2006-04-04 Tripep Ab Hepatitis C virus codon optimized non-structural NS3/4A fusion gene
JP4299540B2 (ja) 2001-01-23 2009-07-22 イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー Ｃ型肝炎ウイルスレプリコンおよびレプリコン増強細胞
US7138376B2 (en) * 2001-09-28 2006-11-21 Idenix Pharmaceuticals, Inc. Methods and compositions for treating hepatitis C virus using 4'-modified nucleosides
EP2172552A3 (en) 2001-10-11 2010-07-21 Merck Sharp & Dohme Corp. Recombinant nucleic acids comprising regions of AD6
JP4475561B2 (ja) * 2001-10-11 2010-06-09 メルク・シャープ・エンド・ドーム・コーポレイション Ｃ型肝炎ウイルスワクチン
DE60326831D1 (en) 2002-04-16 2009-05-07 Merck & Co Inc Hepatitis-c-virus-testsysteme
ATE452192T1 (de) * 2003-02-13 2010-01-15 Merck & Co Inc Verfahren zur vermittlung von zellkulturreplikationsaktivität an unterschiedliche hepatitis-c-virus-isolate
US7414031B2 (en) * 2004-11-22 2008-08-19 Genelabs Technologies, Inc. 5-nitro-nucleoside compounds for treating viral infections
AP2007004128A0 (en) * 2005-02-28 2007-08-31 Genelabs Tech Inc Tricyclic-nucleoside compounds for treating viral infections
US7834145B2 (en) * 2005-03-22 2010-11-16 Merck Sharp & Dohme Corp. HCV protease substrates
WO2006116557A1 (en) * 2005-04-25 2006-11-02 Genelabs Technologies, Inc. Nucleoside compounds for treating viral infections
EP1910337A2 (en) * 2005-06-24 2008-04-16 Genelabs Technologies, Inc. Heteroaryl derivatives for treating viruses
DK1945797T3 (da) * 2005-10-28 2012-08-06 Boehringer Ingelheim Int Hepatitis C-virus NS2/3-aktivitetsanalyse
WO2007145894A2 (en) 2006-06-08 2007-12-21 Merck & Co., Inc. A rapid method to determine inhibitor sensitivity of ns3/4a protease sequences
PE20081113A1 (es) * 2006-07-20 2008-10-03 Genelabs Tech Inc Inhibidores virales policiclicos
US20100216161A1 (en) * 2009-02-26 2010-08-26 Vertex Pharmaceuticals Incorporated Method for identifying protease inhibitors
EP2118301A4 (en) 2007-03-09 2011-04-20 Merck Sharp & Dohme IN VIVO RESISTANCE OF HCV TO ANTI-VIRAL INHIBITORS
EP2185195A2 (en) 2007-08-16 2010-05-19 Tripep Ab Immunogen platform
WO2009029729A1 (en) * 2007-08-31 2009-03-05 Genelabs Technologies, Inc. Amino tricyclic-nucleoside compounds, compositions, and methods of use
AR082453A1 (es) 2010-04-21 2012-12-12 Novartis Ag Compuestos de furopiridina, composiciones farmaceuticas que los contienen y usos de los mismos
AU2011281546B2 (en) 2010-07-22 2014-07-10 Novartis Ag 2,3,5-trisubstituted thiophene compounds and uses thereof
WO2012092484A2 (en) 2010-12-29 2012-07-05 Inhibitex, Inc. Substituted purine nucleosides, phosphoroamidate and phosphorodiamidate derivatives for treatment of viral infections
WO2014139587A1 (en) 2013-03-15 2014-09-18 Okairòs Ag Improved poxviral vaccines
WO2017025782A1 (en) 2014-09-17 2017-02-16 Glaxosmithkline Biologicals Sa Improved poxviral vaccines
US11965191B2 (en) 2018-01-18 2024-04-23 California Institute Of Technology Programmable protein circuits in living cells
US10899823B2 (en) 2018-01-18 2021-01-26 California Institute Of Technology Programmable protein circuits in living cells
US11453893B2 (en) 2018-08-30 2022-09-27 California Institute Of Technology RNA-based delivery systems with levels of control
WO2020047320A1 (en) 2018-08-31 2020-03-05 California Institute Of Technology Synthetic protein circuits detecting signal transducer activity
EP3908653A4 (en) 2019-01-10 2022-11-02 California Institute of Technology SYNTHETIC SYSTEM FOR TUNABLE PROTEIN SIGNAL THRESHOLD

Also Published As

Publication number Publication date
EP0746333B1 (en) 1999-05-06
WO1995022985A1 (en) 1995-08-31
AU691259B2 (en) 1998-05-14
JPH10500005A (ja) 1998-01-06
ES2132644T3 (es) 1999-08-16
ITRM940092A0 (it) 1994-02-23
ATE179611T1 (de) 1999-05-15
CA2182521C (en) 1999-07-06
CA2182521A1 (en) 1995-08-31
ITRM940092A1 (it) 1995-08-23
US5739002A (en) 1998-04-14
RU2149185C1 (ru) 2000-05-20
DK0746333T3 (da) 1999-11-01
JP3280384B2 (ja) 2002-05-13
HK1010988A1 (en) 1999-07-02
GR3030166T3 (en) 1999-08-31
DE69509504D1 (de) 1999-06-10
DE69509504T2 (de) 1999-09-02
BR9506931A (pt) 1997-09-09
AU1822395A (en) 1995-09-11
EP0746333A1 (en) 1996-12-11

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