KR880007729A - 히루딘의 변종과 그 용도 및 그 제조방법 - Google Patents

히루딘의 변종과 그 용도 및 그 제조방법 Download PDF

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KR880007729A
KR880007729A KR870013708A KR870013708A KR880007729A KR 880007729 A KR880007729 A KR 880007729A KR 870013708 A KR870013708 A KR 870013708A KR 870013708 A KR870013708 A KR 870013708A KR 880007729 A KR880007729 A KR 880007729A
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hirudin
glu
gly
asn
variant
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KR870013708A
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KR960011918B1 (ko
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꼬르또니 미셸
데그리스 에릭
롸송 제랄
레므왕 이브
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에띠엥느 아이셍망
트랑젠느 소시에떼아노님
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    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81Protease inhibitors
    • C07K14/815Protease inhibitors from leeches, e.g. hirudin, eglin
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C12P21/00Preparation of peptides or proteins
    • C12P21/02Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

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Abstract

내용 없음.

Description

히루딘의 변종과 그 용도 및 그 제조방법
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 설명책자들에 의해 알려진 3가지 자연성 히루딘 변종의 시 스의 비교표.
제2도는 히루딘 또는 그 변종들을 산출시키기 위한 효모균 배양물의 상징액 분량을 기준으로 한 트롬빈의 코로모자임에 대한 단백분해 활성도 억제율을 도시하는 그라프도.

Claims (13)

  1. 위치 47 또는 위치 63에 있어서 자연형태의 아미노산과는 단른 아미노산을 포함하는 변종.
  2. 제1항에 있어서, 자연형태에서 위치 63의 아미노산 Tyr이 산성 잔존물 Glu 또는 Asp로 대치되는 것을 특징으로 하는 히루딘 변종.
  3. 제1항 및 제2항 중 어느 하나에 있어서, 히루딘 HV1, HV2 또는 HV3의 한 변종인 것을 특징으로 하는 히루딘 변종.
  4. 제1항 내지 제3항 중 어느 하나에 있어서, 자연형태에서 위치 47의 아미노산이 Arg 또는 His에 의해 대치되는 것을 특징으로 하는 히루딘 변종.
  5. 제1항 내지 제3항 중 어느 하나에 있어서, HV2의 자연형태의 아미노산 47번인 Asn이 Lys에 의해 대치되는 것을 특징으로 하는 히루딘 변종.
  6. (Lys47)HV2, (Arg47)HV2, (His47)HV2, (Glu63)HV2, 및 (Asp63)HV2 등에서 선택되는 것을 특징으로 하는 히루딘 변종.
  7. 다음 시 스에 해당하는 히루딘 변종 :
    ILE THR TYR THR ASP CYS THR GLU SER GLY GLN ASN LEU CYS LEU CYS GLU GLY SER ASN VAL CYS GLY LYS GLY ASN LYS CYS ILE LEU GLY SER ASN GLY LYS GLY ASN GLN CYS VAL THR GLY GLU GLY THR PRO LYS PRO GLU SER HIS ASN ASN GLY ASP PHE GLU GLU ILE PRO GLU GLU TYR LEU GLN.
  8. 제1항 내지 제7항 중 어느 하나에 있어서 황산화되거나 또는 그렇지 않은 히루딘 변종.
  9. 트롬빈 억제제로서, 제1항 내지 제8항 중에 히루딘 변종으로 된 트롬빈 억제제.
  10. 항 응혈제로서, 제1항 내지 제8항 중 어느 하나에 의한 최소한 하나의 히루딘 변종을 활성성분으로서 포함하는 조성물.
  11. 의약제품으로서, 제1항 내지 제8항 중 어느 하나에 의한 히루딘 변종으로 된 의약제품.
  12. 히루딘 변종의 제조방법으로서, 합성단계, 반합성 제조단계, 및/또는 유전공학적 시행단계 등이 수반하는 것을 특징으로 하는 제1항 내지 제8항 중 어느 하나에 의한 히루딘 변종을 제조하는 방법.
  13. 제12항에 있어서, 플라스미드나 도는 기능적 DNA 블록으로서 사전에 혈질전환시킨 효모균의 발효로서 구성되며, 상기 플라스미드는 효모균의 2μ 플라스미드의 모사원을 포함하며 ura3 유전자를 포함하며, 대장균내의 모사원 및 항생제에 대한 저항성 마아커를 포함하며, 알파인자의 전구물체의 프리프로 시 스들은 히루딘 변종의 정보시 스의 상류에서 페이스에 맞게 융합되어 있으며, 상기 변종의 유전자의 하류에 위치하는 효모균 PGK 유전자의 전사단말을 포함하며, 상기 기능적 DNA 블록은 상기 히루딘 변종의 정보를 담고 있는 것을 특징으로 하는, 히루딘 변종의 제조방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019870013708A 1986-12-01 1987-12-01 히루딘의 변이체와 그 용도 및 제조방법 KR960011918B1 (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR8616723 1986-12-01
FR16723 1986-12-01
FR868616723A FR2607517B2 (fr) 1986-12-01 1986-12-01 Vecteurs d'expression de variants de l'hirudine dans les levures, procede et produit obtenu

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KR880007729A true KR880007729A (ko) 1988-08-29
KR960011918B1 KR960011918B1 (ko) 1996-09-04

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KR1019870013708A KR960011918B1 (ko) 1986-12-01 1987-12-01 히루딘의 변이체와 그 용도 및 제조방법

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US (1) US5650301A (ko)
EP (1) EP0273800B1 (ko)
JP (1) JP2567263B2 (ko)
KR (1) KR960011918B1 (ko)
AT (1) ATE73462T1 (ko)
AU (1) AU617989B2 (ko)
BG (1) BG49719A3 (ko)
CA (1) CA1341416C (ko)
CS (1) CS276245B6 (ko)
DE (1) DE3777367D1 (ko)
DK (1) DK173247B1 (ko)
ES (1) ES2032465T3 (ko)
FI (1) FI99211C (ko)
FR (1) FR2607517B2 (ko)
GR (1) GR3004556T3 (ko)
HU (1) HU213871B (ko)
IE (1) IE60544B1 (ko)
MC (1) MC1884A1 (ko)
NO (1) NO177500C (ko)
PL (1) PL157254B1 (ko)
PT (1) PT86233B (ko)
RO (1) RO106890B1 (ko)
SU (1) SU1687032A3 (ko)
ZA (1) ZA879011B (ko)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2628429B1 (fr) * 1988-03-08 1990-12-28 Transgene Sa Variants de l'hirudine, leurs utilisations et les procedes pour les obtenir
GB8817161D0 (en) * 1988-07-19 1988-08-24 Ciba Geigy Ag Modified proteins
GB8817160D0 (en) * 1988-07-19 1988-08-24 Ciba Geigy Ag Novel proteins
US5284768A (en) * 1988-08-24 1994-02-08 Sanofi Signal peptide, DNA sequences coding for the latter, expression vectors carrying one of these sequences, gram-negative bacteria transformed by these vectors, and process for the periplasmic production of a polypeptide
US5879926A (en) * 1989-03-31 1999-03-09 Transgene S.A. Yeast strains for the production of mature heterologous proteins, especially hirudin
FR2645174B1 (fr) * 1989-03-31 1994-01-07 Transgene Sa Souches de levure ameliorees pour la production de proteines heterologues matures en particulier d'hirudine et procede de preparation d'hirudine correspondant
FR2645175B1 (fr) * 1989-03-31 1994-02-18 Transgene Sa Souche de saccharomyces cerevisiaeproductrice d'une proteine heterologue et procede de preparation de ladite proteine heterologue par fermentation de ladite souche
FR2646437B1 (fr) * 1989-04-28 1991-08-30 Transgene Sa Nouvelles sequences d'adn, leur application en tant que sequence codant pour un peptide signal pour la secretion de proteines matures par des levures recombinantes, cassettes d'expression, levures transformees et procede de preparation de proteines correspondant
FR2656531B1 (fr) * 1989-12-29 1992-04-24 Sanofi Sa Promoteur artificiel pour l'expression de proteines dans le levure.
US5118790A (en) * 1990-07-24 1992-06-02 Sri International Analogs of hirudin
ATE140929T1 (de) * 1990-11-08 1996-08-15 Japan Energy Corp Hirudinmutante, deren herstellung, antikoagulans, sekretorischer vektor, durch besagten vektor transformierter mikroorganismus und herstellung eines produkts durch besagten mikroorganismus
US5837808A (en) * 1991-08-20 1998-11-17 Baxter International Inc. Analogs of hirudin
US5407822A (en) * 1991-10-02 1995-04-18 Sanofi Artificial promoter for the expression of proteins in yeast
JP7375012B2 (ja) * 2019-04-16 2023-11-07 サンゲン バイオサイエンス カンパニー,リミテッド ヒルジン突然変異体の抽出・精製方法およびその使用

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1341417C (fr) * 1984-03-27 2003-01-21 Paul Tolstoshev Vecteurs d'expression de l'hirudine, cellules transformees et procede de preparation de l'hirudine
EP0168342B1 (de) * 1984-06-14 1991-07-03 Ciba-Geigy Ag Verfahren zur Herstellung von Thrombin-Inhibitoren
DE3429430A1 (de) * 1984-08-10 1986-02-20 Hoechst Ag, 6230 Frankfurt Gentechnologisches verfahren zur herstellung von hirudin und mittel zur durchfuehrung dieses verfahrens
DE3445517C2 (de) * 1984-12-13 1993-11-18 Ciba Geigy Für ein Hirudin-ähnliches Protein codierende DNA-Sequenz und Verfahren zur Herstellung eines Hirudin-ähnlichen Proteins
FR2593518B1 (fr) * 1985-05-02 1989-09-08 Transgene Sa Vecteurs d'expression et de secretion de l'hirudine par les levures transformees
DE3689525D1 (de) * 1985-07-17 1994-02-24 Hoechst Ag Neue Polypeptide mit blutgerinnungshemmender Wirkung, Verfahren zu deren Herstellung bzw. Gewinnung, deren Verwendung und diese enthaltende Mittel.

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Publication number Publication date
AU617989B2 (en) 1991-12-12
FI99211C (fi) 1997-10-27
NO874905D0 (no) 1987-11-25
CS276245B6 (en) 1992-05-13
BG49719A3 (en) 1992-01-15
DK173247B1 (da) 2000-05-22
EP0273800A2 (fr) 1988-07-06
PT86233B (pt) 1990-11-07
PT86233A (fr) 1987-12-01
ATE73462T1 (de) 1992-03-15
DE3777367D1 (de) 1992-04-16
HUT45564A (en) 1988-07-28
FR2607517B2 (fr) 1989-12-22
GR3004556T3 (ko) 1993-04-28
JPS63152987A (ja) 1988-06-25
IE60544B1 (en) 1994-07-27
ZA879011B (en) 1988-05-27
CA1341416C (fr) 2003-01-21
EP0273800B1 (fr) 1992-03-11
CS8708732A2 (en) 1991-07-16
NO874905L (no) 1988-06-02
KR960011918B1 (ko) 1996-09-04
NO177500C (no) 1995-09-27
MC1884A1 (fr) 1989-01-24
DK627687D0 (da) 1987-11-30
FR2607517A2 (fr) 1988-06-03
FI875295A0 (fi) 1987-12-01
ES2032465T3 (es) 1993-02-16
PL269164A1 (en) 1988-08-18
HU213871B (en) 1997-11-28
FI99211B (fi) 1997-07-15
PL157254B1 (pl) 1992-05-29
DK627687A (da) 1988-06-02
JP2567263B2 (ja) 1996-12-25
US5650301A (en) 1997-07-22
SU1687032A3 (ru) 1991-10-23
EP0273800A3 (en) 1988-07-20
RO106890B1 (ro) 1993-07-30
IE873239L (en) 1988-06-01
FI875295A (fi) 1988-06-02
AU8188087A (en) 1988-06-02
NO177500B (no) 1995-06-19

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