DE3722673A1 - DNA coding for plasminogen activator inhibitor type 2 (PAI-2) - Google Patents

DNA coding for plasminogen activator inhibitor type 2 (PAI-2)

Info

Publication number
DE3722673A1
DE3722673A1 DE19873722673 DE3722673A DE3722673A1 DE 3722673 A1 DE3722673 A1 DE 3722673A1 DE 19873722673 DE19873722673 DE 19873722673 DE 3722673 A DE3722673 A DE 3722673A DE 3722673 A1 DE3722673 A1 DE 3722673A1
Authority
DE
Germany
Prior art keywords
pai
dna
plasminogen activator
activator inhibitor
cdna
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.)
Withdrawn
Application number
DE19873722673
Other languages
German (de)
Inventor
Tor Dr Ny
Ingegerd Dr Lecander
Birger Prof Astedt
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.)
Siemens Healthcare Diagnostics GmbH Germany
Original Assignee
Behringwerke AG
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 DE19873713272 external-priority patent/DE3713272A1/en
Application filed by Behringwerke AG filed Critical Behringwerke AG
Priority to DE19873722673 priority Critical patent/DE3722673A1/en
Publication of DE3722673A1 publication Critical patent/DE3722673A1/en
Withdrawn legal-status Critical Current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
    • C07K14/8121—Serpins
    • C07K14/8132—Plasminogen activator inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/38—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against protease inhibitors of peptide structure
    • 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
    • G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/81—Protease inhibitors
    • G01N2333/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • G01N2333/811—Serine protease (E.C. 3.4.21) inhibitors
    • G01N2333/8121—Serpins
    • G01N2333/8132—Plasminogen activator inhibitors

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

With the aid of a cDNA which codes for most of plasminogen activator inhibitor type 2 (PAI-2) the cDNA which codes for the complete molecule was found. This cDNA can be used not only to obtain PAI-2 by genetic manipulation in high purity, but also to prepare diagnostic aids which allow the analysis of genetic PAI-2 defects. Furthermore, it is possible on the basis of the complete amino-acid sequence to prepare antibodies which are suitable for diagnostic aids and antibody affinity columns.

Description

Zusatz zur deutschen Patentanmeldung P 37 13 272.5Addendum to German patent application P 37 13 272.5

Die Hauptanmeldung betrifft eine DNA-Sequenz, codierend für Plasminogenaktivator-Inhibitor, Typ 2 (PAI-2), enthaltend den codierenden Strang gemäß Tabelle 1 der Hauptanmeldung, sowie DNA, die mit dieser DNA hybridisiert, und auch DNA-Sequenzen, die für die Aminosäuresequenz in der genannten Tabelle 1 codieren. Die Hauptanmeldung betrifft weiterhin Genstrukturen, die eine solche DNA enthalten, Vektoren, die eine solche DNA-Sequenz enthalten, transformierte Zellen, die eine solche DNA enthalten, ein Rohprotein, das von einer solchen transformierten Zelle exprimiert wird und PAI-2, das aus einem derartigen Rohprotein erhalten wird. Weiterhin betrifft die Hauptanmeldung PAI-2, erhalten durch Expression in Bakterien, Hefen oder Säugerzellen, ein Protein mit PAI-2-Aktivität, enthaltend die Aminosäuresequenz gemäß Tabelle 1 der Hauptanmeldung oder Teilen dieser Aminosäuresequenz, sowie Mutanten und Varianten dieser Proteine. Ein weiterer Aspekt der Hauptanmeldung betrifft für PAI-2 spezifische Antikörper, erhalten aus gentechnischen hergestelltem PAI-2 bzw. Antigenwirksamen Teilen davon sowie ein Diagnostikum, das ein solches Antigen enthält bzw. ein Diagnostikum, das eine wie vorstehend charakterisierte DNA ganz oder teilweise enthält. Außerdem bezieht sich die Hauptanmeldung auf Diagnostizierverfahren, bei denen Körperflüssigkeiten, Gewebe oder daraus isolierte Nukleinsäuren mit einem der genannten Diagnostika in Kontakt gebracht werden. Weiterhin bezieht sich die Hauptanmeldung auf Arzneimittel, die durch einen Gehalt an einem der vorstehend charakterisierten Proteine gekennzeichnet sind. The main application relates to a DNA sequence coding for Containing plasminogen activator inhibitor, type 2 (PAI-2) the coding strand according to Table 1 of the main application, as well as DNA that hybridizes with this DNA, and also DNA sequences, those for the amino acid sequence mentioned in the Code Table 1. The main application continues to concern Gene structures that contain such DNA, vectors, which contain such a DNA sequence Cells that contain such DNA, a crude protein that is expressed by such a transformed cell and PAI-2, which is obtained from such a crude protein. The parent application further relates to PAI-2, obtained by Expression in bacteria, yeast or mammalian cells Protein with PAI-2 activity containing the Amino acid sequence according to Table 1 of the main application or Parts of this amino acid sequence, as well as mutants and Variants of these proteins. Another aspect of Main application concerns antibodies specific for PAI-2, obtained from genetically engineered PAI-2 or antigenic Parts of it, as well as a diagnostic, the one contains such an antigen or a diagnostic agent that a like All or part of the DNA characterized above contains. The main application also relates to Diagnostic procedures in which body fluids, Tissue or nucleic acids isolated therefrom with one of the mentioned diagnostics are brought into contact. Farther The main filing relates to medicinal products caused by a content of one of those characterized above Proteins are labeled.  

Die Tabelle 1 der Hauptanmeldung charakterisiert eine DNA-Sequenz, die für die 361 C-terminalen Aminosäuren von PAI-2 codiert. Unter Verwendung dieser DNA als Sonde wurde in einer cDNA-Bibliothek gemäß Hauptanmeldung die komplette cDNA-Sequenz isoliert und charakterisiert, die für alle 415 Aminosäuren von PAI-2 codiert. Diese komplette DNA-Sequenz und die abgeleitete Aminosäure-Sequenz sind in der Tabelle 1 wiedergegeben.Table 1 of the main application characterizes a DNA sequence those for the 361 C-terminal amino acids of PAI-2 coded. Using this DNA as a probe, in a cDNA library according to the main application cDNA sequence isolated and characterized for all 415 Amino acids encoded by PAI-2. This complete DNA sequence and the deduced amino acid sequence are in the table 1 reproduced.

Von dem von R. D. Ye et al., J. Biol. Chem. 262 (1987) 3718-3725, beschriebenen Plasminogenaktivator-Inhibitor aus humaner Plazenta unterscheidet sich der erfindungsgemäße Inhibitor durch die folgenden drei unterschiedlichen Aminosäuren: In Position 120 und 404 steht Asn anstelle von Asp bzw. Lys und in Position 414 steht Ser anstelle von Cys. Darüber hinaus unterscheidet sich die DNA im Bereich des Tripletts für Pro in Position 393, wo die erfindungsgemäße cDNA CCT anstelle von CCG enthält.From that of R. D. Ye et al., J. Biol. Chem. 262 (1987) 3718-3725, described plasminogen activator inhibitor human placenta differs from that of the invention Inhibitor by the following three different ones Amino acids: Asn is in position 120 and 404 of Asp or Lys and in position 414 Ser stands for Cys. In addition, the DNA differs in area of the triplet for Pro in position 393, where the contains cDNA CCT according to the invention instead of CCG.

Außerdem finden sich weitere Unterschiede in der nichttranslatierten DNA.There are also other differences in the non-translated DNA.

Die experimentelle Ausführung erfolgte entsprechend den in der Hauptanmeldung enthaltenen Beispielen.The experimental execution was carried out according to the in of the main application.

Claims (12)

1. DNA-Sequenz, codierend für Plasminogenaktivator-Inhibitor, Typ 2 (PAI-2), enthaltend den codierenden Strang gemäß Tabelle 1.1. DNA sequence coding for plasminogen activator inhibitor, Type 2 (PAI-2) containing the coding Strand according to table 1. 2. DNA-Sequenz, codierend für die Aminosäuresequenz gemäß Tabelle 1.2. DNA sequence coding for the amino acid sequence according to Table 1. 3. Genstruktur, enthaltend eine DNA gemäß Anspruch 1 oder 2.3. gene structure containing a DNA according to claim 1 or 2nd 4. Vektor, enthaltend eine DNA-Sequenz nach einem oder mehreren der vorhergehenden Ansprüche.4. Vector containing a DNA sequence after one or several of the preceding claims. 5. Transformierte Zelle, enthaltend DNA nach Anspruch 1, 2 oder 3.5. Transformed cell containing DNA according to claim 1, 2 Or 3. 6. Rohprotein, exprimiert von einer Zelle gemäß Anspruch 5.6. crude protein expressed by a cell according to claim 5. 7. PAI-2, erhalten aus einem Rohprotein gemäß Anspruch 6.7. PAI-2 obtained from a crude protein according to claim 6. 8. PAI-2-spezifische Antikörper, erhalten aus einem Protein nach Anspruch 7.8. PAI-2 specific antibodies obtained from one Protein according to claim 7. 9. Diagnostikum, enthaltend einen Antikörper nach Anspruch 8.9. Diagnostic agent containing an antibody according to claim 8th. 10. Diagnostikum, das eine DNA nach Anspruch 1 oder 2 enthält.10. Diagnostic agent, which is a DNA according to claim 1 or 2 contains. 11. Diagnostizierverfahren, dadurch gekennzeichnet, daß Körperflüssigkeit, Gewebe oder daraus isolierte Nukleinsäuren mit einem Diagnostikum nach Anspruch 9 oder 10 in Kontakt gebracht werden. 11. Diagnostic method, characterized in that Body fluid, tissue or isolated from it Nucleic acids with a diagnostic agent according to claim 9 or 10 are brought into contact.   12. Arzneimittel, gekennzeichnet durch einen Gehalt an einem Protein nach Anspruch 7.12. Medicinal product characterized by a content of a protein according to claim 7.
DE19873722673 1987-04-18 1987-07-09 DNA coding for plasminogen activator inhibitor type 2 (PAI-2) Withdrawn DE3722673A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE19873722673 DE3722673A1 (en) 1987-04-18 1987-07-09 DNA coding for plasminogen activator inhibitor type 2 (PAI-2)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19873713272 DE3713272A1 (en) 1987-04-18 1987-04-18 Plasminogen activator inhibitor type 2 (PAI-2)
DE19873722673 DE3722673A1 (en) 1987-04-18 1987-07-09 DNA coding for plasminogen activator inhibitor type 2 (PAI-2)

Publications (1)

Publication Number Publication Date
DE3722673A1 true DE3722673A1 (en) 1989-01-19

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Family Applications (1)

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DE19873722673 Withdrawn DE3722673A1 (en) 1987-04-18 1987-07-09 DNA coding for plasminogen activator inhibitor type 2 (PAI-2)

Country Status (1)

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DE (1) DE3722673A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991003556A1 (en) * 1989-09-05 1991-03-21 Biotechnology Australia Pty Ltd Recombinant product
WO1991009124A1 (en) * 1989-12-20 1991-06-27 Biotech Australia Pty. Limited Variants of pai-2

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991003556A1 (en) * 1989-09-05 1991-03-21 Biotechnology Australia Pty Ltd Recombinant product
US5298400A (en) * 1989-09-05 1994-03-29 Biotechnology Australia Pty. Ltd. Polynucleotide constructs for secreted glycosylated plasminogen activator inhibitor-2 (PAI-2)
WO1991009124A1 (en) * 1989-12-20 1991-06-27 Biotech Australia Pty. Limited Variants of pai-2
AU625018B2 (en) * 1989-12-20 1992-06-25 Biotech Australia Pty Limited Variants of pai-2
US5444153A (en) * 1989-12-20 1995-08-22 Biotech Australia Pty Limited Variants of PAI-2

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