KR840006369A - 생물학적 활성 단백질의 합성 뮤테인의 제조방법 - Google Patents

생물학적 활성 단백질의 합성 뮤테인의 제조방법 Download PDF

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KR840006369A
KR840006369A KR1019830004927A KR830004927A KR840006369A KR 840006369 A KR840006369 A KR 840006369A KR 1019830004927 A KR1019830004927 A KR 1019830004927A KR 830004927 A KR830004927 A KR 830004927A KR 840006369 A KR840006369 A KR 840006369A
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에프 마크 데이비드
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미카엘 에스 오스트라크
세투스 코포레이션
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Abstract

내용 없음

Description

생물학적 활성 단백질의 합성 뮤테인의 제조방법
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 IFN-β의 아미노산2서열도이고,
제2도는 올리고뉴클레오티드 표적 돌연변이에 의한 돌연변이성 IFN-β 유전자 제조의 모식도이며,
제3도는 IFN-β유저자를 함유하는 플라스미드 pβ1trp도이고,
제4도는 클로닝 벡터 M13mp 8파지(cloning vcctor M13mp8 pharge)도.

Claims (32)

  1. 디설파이드 결합을 할 수 있고 생물학적 활성을 나타내는데에 비필수적인 시스테인 잔기 한개 이상을 함유하며 이 시스테인 잔기중 적어도 하나는 제거되거나 다른 이미노산으로 치환된 생물학적으로 활성인 단백질의 합성 뮤테인을 제조하는 방법에 있어서 합성뮤테인을 코드하는 구조적 유전다를 함유하는 표현형백터로써 형질 전환된 제조합 숙주세포 또는 미생물. 또는 이와같은 세포 또는 미생물의 자손을 배양시킨 다음 이 배양물로부터 생성된 합성뮤테인을 수득함을 특징으로 하는 방법.
  2. 제1항에 있어서, 시스테인 잔기가 단지 한개인 방법.
  3. 제1항에 있어서, 시스테인 잔기가 세린, 트레오닌, 글리신, 알리닌, 발린, 루신, 이소루신, 히스티딘, 티로신, 페닐알라닌, 트립토판 또는 메티오닌으로 치환된 방법.
  4. 제1항에 있어서, 시스테인 잔기가 세린 또는 트레오닌으로 치환된 방법.
  5. 제1항에 있어서, 단백질이 IFN-β, IL-2, 림포톡신, 집락 자극 인자-1 또는 IFN-α 1인 방법.
  6. 제1항에 있어서, 단백질이 IFN-β이고, 시스테인 잔기가 IFN-β의 17위치이며, 시스테인잔기가 세린 잔기로 치환된 방법.
  7. 제6항에 있어서, 뮤테인이 비글리코실화된 방법.
  8. 제1항에 있어서, 단백질이 IL-2이고, 시스테인 잔기가 IL-2의 125위치이며, 시스테인 잔기가 세린으로 치환된 방법.
  9. 제8항에 있어서, 뮤테인이 비글리코실화된 방법.
  10. 디설파이드 결합을 형성할 수 있으며, 생물학적 활성을 나타내는데 비필수적인 시스테인 잔기 한개 이상을 함유하며 이 시스테인 잔기중 적어도 하나는 제거되거나 다른 아미노산으로 치환된 생물학적 활성 단백질의 합성 뮤테인을 코드하는 구조적 유전자를 함유하는 표현형 벡터로써 형질전환 됨을 특징으로 하는 재조합 세포 또는 미생물 및 이들의 자손.
  11. 제10항에 있어서, 시스테인 잔기가 한개만 존재함을 특징으로 하는 재조합 세포 또는 미생물.
  12. 제10항에 있어서 시스테인 잔기가 세린, 트레오닌, 글리신, 알라닌, 발린, 루신, 이소루신, 히스티딘, 티로신, 페닐알라닌, 트립토판 또는 메티오닌으로 치환됨을 특징으로 하는 재조합 세포또는 미생물.
  13. 제10항에 있어서, 시스테인 잔기가 세린 또는 트레오닌으로 치환됨을 특징으로 하는 재조합 세포 또는 미생물.
  14. 제10항에 있어서, 단백질이 IFN-β, IL-2, 림포톡신, 집락 자극 인자-1 또는 IFN-α1임을 특징으로 하는 재조합 세포 또는 미생물.
  15. 제10항에 있어서, 단백질이 IFN-β이고, 시스테인 잔기가 IFN-β의 17위치이며, 시스테인 잔기가 세린 잔기로 치환됨을 특징으로 하는 재조합세포 또는 미생물.
  16. 제15항에 있어서, 뮤테인을 비글리코실화함을 특징으로 하는 재조합 세포 또는 미생물.
  17. 제10항에 있어서, 단백질이 IL-2이고, 시스테인 잔기가 IL-2의 125위치이며, 시스테인 잔기가 세린으로 치환됨을 특징으로 하는 재조합세포 또는 미생물.
  18. 제17항에 있어서, 뮤테인을 비글리코실화함을 특징으로 하는 재조합 세포 또는 미생물.
  19. 시스테인 잔기를 제거하거나 다른 아미노산으로 치환함으로써 단백질을 돌연변이 시킴을 특징으로 하여 디설파이드 결합을 할 수 있는 시수테인 잔기 한개 이상을 함유하는 단백질의 디설파이드 결합을 방지하는 방법.
  20. 제19항에 있어서, 단백질이 생물학적으로 활성이며, 시스테인이 생물학적 활성을 나타내는데 필수적이 아님을 특징으로 하는 방법.
  21. 제19항 또는 20항에 있어서, 시스테인 잔기를 세린 또는 트레오닌으로 치환함을 특징으로 하는 방법.
  22. 제19항에 있어서, 단백질이 IFN-β, IL-2, 림포톡신, 집락 자극 인자-1 또는 IFN-α1임을 특징으로 하는 방법.
  23. 제19항에 있어서, 단백질이 IFN-β이고, 시스테인 잔기가 IFN-β의 17위치이며, 시스테인 잔기를세린으로 치환함을 특징으로 하는 방법.
  24. 제19항에 있에서 단백질이 IL-2이고, 시스테인 잔기가 IL-2의 125위치이며, 시스테인 잔기를 세린으로 치환함을 특징으로 하는 방법.
  25. (a) 디설파이드 결합을 형성할 수 있으며, 생물학적 활성을 나타내는데에 비필수적인 시스테인 잔기 한개 이상을 함유하는 생물학적으로 활성인 단백질을 코드하는 구조적 유전자의 나선을 함유하는 단일 나선의 DNA를 , 시스테인 잔기에 대한 코돈을 함유하는 나선부위 또는 이 코돈과 짝지워진 항감작 삼중체에 보족적인 돌연변이성 올리고 뉴클레오티드 프라이머로 하이브리드화하고, (경우에 따라, 다른 아미노산에 대해 코드하는 코돈 또는 삼중체를 제거함을 뜻하는 코돈 또는 항감작삼중체와의 미스 매취는 제외됨) (b)이 프라이머를 DNA 폴리멀라아제와 연장시켜 돌연변이성 헤테로 이중체를 형성하며, (c) 돌연변이 성헤테로 이중체를 복제함을 특징으로 하여 제거되거나 다른 아미노산으로 치환된 한개 이상의 시스테인 잔기를 함유하는 언급된 생물학적으로 활성인 단백질의 합성 뮤테인을 코드하는 유전자를 제조하는 방법.
  26. 제25항에 있어서, 미스매취가 세린 또는 메티오닌에 대한 코드인 삼중체(triplet)임을 특징으로 하는 방법.
  27. 제25항에 있어서, 단일나선 DNA가 나선을 함유하는 단일 나선 파지이며, (b)단계의 돌연변이성 헤테로 이중체를 폐환된 헤테로 이중체로 전환시킴을 특징으로 하는 방법.
  28. 제25항에 있어서, 폐환 헤테로 이중체로 적합한 세균 숙주를 형질 전환시킨다음, 생성된 형질 전환체를 배양함으로써 복제를 수행함을 특징으로 하는 방법.
  29. 제25항에 있어서, 헤테로 이중체의 돌연변이 나선의 자손을 분리한 다음, 이 자손으로부터 DNA를 분리하고, 다시 이 DNA로 부터 유전자를 분리하는 추가의 단계가 포함됨을 특징으로 하는 방법.
  30. 제 25,26,27,28 또는 29항에 있어서, 단백질이 인체 IFN-β이고, 시스테인 잔기가 17위치이며, 미스매취가 세린에 대한 코돈임을 특징으로 하는 방법.
  31. 제29항에 있어서, 나선이 IFN-β에 항감작 나선이고, 돌연변이 올리고 뉴클레오티드 프라이머가 GCAATTTTCAGAGTCAG임을 특징으로 하는 방법.
  32. 제 25,26,27,28 또는 29항에 있어서, 단백질이 인체 IL-2이며, 시스테인 잔기가 125위치이고, 미스매취가 세린에 대한 코돈임을 특징으로 하는 방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019830004927A 1982-10-19 1983-10-18 생물학적 활성 단백질의 합성 뮤테인 및 이의 제조방법 KR910009900B1 (ko)

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US43515482A 1982-10-19 1982-10-19
US435154 1982-10-19
US48616283A 1983-04-15 1983-04-15
US486,162 1983-04-15

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KR840006369A true KR840006369A (ko) 1984-11-29
KR910009900B1 KR910009900B1 (ko) 1991-12-03

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EP0234599A1 (en) 1987-09-02
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NO833793L (no) 1984-04-24
EP0109748A1 (en) 1984-05-30
NO173740B (no) 1993-10-18
ES8608043A1 (es) 1986-06-01
EP0192811A1 (en) 1986-09-03
FR2534594B1 (fr) 1987-06-19
FI82266B (fi) 1990-10-31
LU88357I2 (fr) 1994-05-04
JPS6420096A (en) 1989-01-24
DE3382197D1 (de) 1991-04-11
ES8506801A1 (es) 1985-08-01
FR2534594A1 (fr) 1984-04-20
DK105892A (da) 1992-08-26
AU563962B2 (en) 1987-07-30
PH20343A (en) 1986-12-04
BE898016A (fr) 1984-02-15
ATE33503T1 (de) 1988-04-15
DK168767B1 (da) 1994-06-06
ATE73493T1 (de) 1992-03-15
IL69970A0 (en) 1984-01-31
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PT77512B (en) 1987-11-24
DK481383D0 (da) 1983-10-19
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EP0234599B1 (en) 1992-03-11
LU88761I2 (fr) 1996-11-05
FI82266C (fi) 1991-02-11
CH669395A5 (ko) 1989-03-15
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ATE46539T1 (de) 1989-10-15
FI833681A (fi) 1984-04-20
LU90413I2 (fr) 1999-09-07
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