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WO2000061634A3 - Ecotin-variant modulators of serine proteases - Google Patents

Ecotin-variant modulators of serine proteases Download PDF

Info

Publication number
WO2000061634A3
WO2000061634A3 PCT/US2000/009790 US0009790W WO0061634A3 WO 2000061634 A3 WO2000061634 A3 WO 2000061634A3 US 0009790 W US0009790 W US 0009790W WO 0061634 A3 WO0061634 A3 WO 0061634A3
Authority
WO
WIPO (PCT)
Prior art keywords
ecotin
serine protease
serine
modulators
variant
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/US2000/009790
Other languages
French (fr)
Other versions
WO2000061634A2 (en
Inventor
Charles S Craik
Robert J Fletterick
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.)
University of California Berkeley
University of California San Diego UCSD
Original Assignee
University of California Berkeley
University of California San Diego UCSD
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 University of California Berkeley, University of California San Diego UCSD filed Critical University of California Berkeley
Priority to AU46433/00A priority Critical patent/AU4643300A/en
Publication of WO2000061634A2 publication Critical patent/WO2000061634A2/en
Publication of WO2000061634A3 publication Critical patent/WO2000061634A3/en
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
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

This invention provides a class binding proteins that specifically bind to polypeptides having a chymotrypsin fold (e.g. serine proteases). When the target polypeptides are serine proteases the binding proteins can act to inhibit or activate the serine protease. The binding proteins are based on the structure of ecotin. It was discovered that modification of the amino or carboxyl terminus and/or randomization of one or more of loops 50s, 60s, 80s or 100s will provide an ecotin variant library from which can be selected binding molecules (e.g. protease modulators) specific to virtually any serine protease. Depending on the ecotin variant and the target serine protease, the modulator can act as a serine protease inhibitor or as a serine protease activator. Specific agonists of Factor IXa are disclosed.
PCT/US2000/009790 1999-04-12 2000-04-12 Ecotin-variant modulators of serine proteases Ceased WO2000061634A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU46433/00A AU4643300A (en) 1999-04-12 2000-04-12 Engineering ecotin-variant modulators of serine proteases

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US29051399A 1999-04-12 1999-04-12
US09/290,513 1999-04-12

Publications (2)

Publication Number Publication Date
WO2000061634A2 WO2000061634A2 (en) 2000-10-19
WO2000061634A3 true WO2000061634A3 (en) 2001-03-08

Family

ID=23116349

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/009790 Ceased WO2000061634A2 (en) 1999-04-12 2000-04-12 Ecotin-variant modulators of serine proteases

Country Status (2)

Country Link
AU (1) AU4643300A (en)
WO (1) WO2000061634A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1800136B1 (en) * 2004-10-15 2011-12-07 Danisco US Inc. Competitive differential screening
CN107135653A (en) * 2014-10-01 2017-09-05 安迅生物制药公司 Colicine variant
CN106226428B (en) * 2016-07-20 2019-01-01 未名生物医药有限公司 A kind of method of recombinant human nerve growth factor content in quick detection Chinese hamster ovary celI fermentation liquid

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5719041A (en) * 1993-09-14 1998-02-17 Genentech, Inc. DNA encoding ecotin homologs

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5719041A (en) * 1993-09-14 1998-02-17 Genentech, Inc. DNA encoding ecotin homologs

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
SEONG E.A.: "Mutational analysis for the role of C-terminal region of ecotin, a dimeric inhibitor of pancreatic serine proteases", BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL, vol. 42, no. 4, July 1997 (1997-07-01), pages 799 - 807, XP000952778 *
WANG CHENG-I ET AL: "Isolation of a High Affinity Inhibitor of Urokinase-type Plasminogen Activator by Phage Display of Ecotin", JOURNAL OF BIOLOGICAL CHEMISTRY,THE AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, INC.,,US, vol. 270, no. 20, 1995, pages 12250 - 12256, XP002146128, ISSN: 0021-9258 *
YANG E.A.: "Ecotin: a serine protease inhibitor with two distinct and interacting binding sites", JOURNAL MOLECULAR BIOLOGY, vol. 279, 19 June 1998 (1998-06-19), pages 945 - 957, XP002150104 *
YANG E.A.: "Engineering bidentate macromolecular inhibitors for trypsin and urokinase-type plasminogen activator", JOURNAL MOLECULAR BIOLOGY, vol. 279, 19 June 1998 (1998-06-19), pages 1001 - 1011, XP002150105 *

Also Published As

Publication number Publication date
AU4643300A (en) 2000-11-14
WO2000061634A2 (en) 2000-10-19

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