KR960706558A - 골 발육 촉진성 단백질의 돌연변이체(mutants of bone morphogenetic proteins) - Google Patents

골 발육 촉진성 단백질의 돌연변이체(mutants of bone morphogenetic proteins)

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KR960706558A
KR960706558A KR1019960703011A KR19960703011A KR960706558A KR 960706558 A KR960706558 A KR 960706558A KR 1019960703011 A KR1019960703011 A KR 1019960703011A KR 19960703011 A KR19960703011 A KR 19960703011A KR 960706558 A KR960706558 A KR 960706558A
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bmp
amino acid
mutant
seq
substituted
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엠. 울프만 네일
멕코이 존
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데스로이져 토마스 제이.
제네틱스 인스티튜트, 인코포레이티드
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    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475Growth factors; Growth regulators
    • C07K14/51Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease

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Abstract

골 발육 촉진성 단백질(BMP)의 돌연변이 형태를 코오딩하는 DNA 분자가 밝혀졌다. -BMP의 돌연변이 형태는 박테리아에 의해 생성될 수 있으며, 생물학적으로 활성이 있는 BMP의 단일이합체 또는 이형이합체를 생성하기 위해 재폴딩 될 수 있다. 또한, 이러한 돌연변이체 BMP를 제조하는 방법이 밝혀졌다.

Description

골 발육 촉진성 단백질의 돌연변이체(MUTANTS OF BONE MORPHOGENETIC PROTEINS)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 BMP-2, 4, 5, 6, 7 및 8의 서열을 비교한 도면이다.

Claims (17)

  1. 319 내지 321의 3 누클레오티드가 아스파르트산을 코오딩하는 3 누클레오티드로 치환된 것을 제외하고는, 서열 ID 번호 : 3에 나타난 바와 같은 BMP-4를 코오딩하는 누클레오티드 서열로 이루어지는 것을 특징으로 하는 재조합 DNA 분자.
  2. 166 내지 168의 3 누클레오티드가 히스티딘을 코오딩하는 3 누클레오티드로 치환된 것을 제외하고는, 서열 ID 번호 : 5에 나타난 바와 같은 BMP-5를 코오딩하는 누클레오티드 서열로 이루어지는 것을 특징으로 하는 재조합 DNA 분자.
  3. 166 내지 168의 3 누클레오티드가 히스티딘을 코오딩하는 3 누클레오티드로 치환된 것을 제외하고는, 서열 ID 번호 : 7에 나타난 바와 같은 BMP-6를 코오딩하는 누클레오티드 서열로 이루어지는 것을 특징으로 하는 재조합 DNA 분자.
  4. 187 내지 189의 3 누클레오티드가 히스티딘을 코오딩하는 3 누클레오티드로 치환된 것을 제외하고는, 서열 ID 번호 : 9에 나타난 바와 같은 BMP-7를 코오딩하는 누클레오티드 서열로 이루어지는 것을 특징으로 하는 재조합 DNA 분자.
  5. 187 내지 189의 3 누클레오티드가 히스티딘을 코오딩하는 3 누클레오티드로 치환된 것을 제외하고는, 서열 ID 번호 : 11에 나타난 바와 같은 BMP-8를 코오딩하는 누클레오티드 서열로 이루어지는 것을 특징으로 하는 재조합 DNA 분자.
  6. 아미노산 107 잔기인 글루탐산이 아스파트산으로 치환된 서열 ID 번호 : 4의 아미노산 서열로 이루어지는 것을 특징으로 하는 돌연변이체 BMP-4의 정제 조성물.
  7. 아미노산 56 잔기인 알라닌이 히스티딘으로 치환된 서열 ID 번호 : 6의 아미노산 서열로 이루어지는 것을 특징으로 하는 돌연변이체 BMP-5의 정제 조성물.
  8. 아미노산 56 잔기인 알라닌이 히스티딘으로 치환된 서열 ID 번호 : 8의 아미노산 서열로 이루어지는 것을 특징으로 하는 돌연변이체 BMP-6의 정제 조성물.
  9. 아미노산 63 잔기인 알라닌이 히스티딘으로 치환된 서열 ID 번호 : 10의 아미노산 서열로 이루어지는 것을 특징으로 하는 돌연변이체 BMP-7의 정제 조성물.
  10. 아미노산 63 잔기인 세린이 히스티딘으로 치환된 서열 ID 번호 : 12의 아미노산 서열로 이루어지는 것을 특징으로 하는 돌연변이체 BMP-8의 정제 조성물.
  11. 제6항에 따른 하나 이상의 돌연변이체 BMP로 이루어지는 것을 특징으로 하는 BMP 이형 이합체의 정제 조성물.
  12. 제7항에 따른 하나 이상의 돌연변이체 BMP로 이루어지는 것을 특징으로 하는 BMP 이형 이합체의 정제 조성물.
  13. 제8항에 따른 하나 이상의 돌연변이체 BMP로 이루어지는 것을 특징으로 하는 BMP 이형 이합체의 정제 조성물.
  14. 제9항에 따른 하나 이상의 돌연변이체 BMP로 이루어지는 것을 특징으로 하는 BMP 이형 이합체의 정제 조성물.
  15. 제10항에 따른 하나 이상의 돌연변이체 BMP로 이루어지는 것을 특징으로 하는 BMP 이형 이합체의 정제 조성물.
  16. 증진된 재폴딩 특성을 갖는 골 발육 촉진성 단백질(BMP)의 돌연변이체를 수득하는 방법으로 : a) 재폴딩이 잘되는 것으로 밝혀진 BMP의 아미노산 서열(BMP+)과 재폴딩이 잘되지 않는 BMP의 아미노산 서열(BMP-)의 비교; b) (a) 단계에서의 비교를 통해 상호 관계가 있는 아미노산 위치에서의 차이를 결정; c) 변형 BMP- 단백질을 형성하기 위해, BMP+의 상호 관계가 있는 아미노산과 차이가 있는 아미노산이 BMP+의 상호 관계가 있는 아미노산으로 치환되도록 BMP-의 아미노산 서열 변경; d) 재폴딩 능력에 대한 BMP- 단백질의 테스트로 이루어지는 것을 특징으로 하는 방법.
  17. 제16항의 방법으로 생성된 증진된 재폴딩 특성을 갖는 골 발육 촉진성 단백질(BMP)의 돌연변이체.
    ※ 참고사항 : 최초출원 내용에 의하여 공개되는 것임.
KR1019960703011A 1993-12-07 1994-11-15 골발육촉진성단백질의돌연변이체 KR100361058B1 (ko)

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PT733108E (pt) 2001-08-30
JPH09506259A (ja) 1997-06-24
WO1995016034A1 (en) 1995-06-15
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US5804416A (en) 1998-09-08
CA2176943A1 (en) 1995-06-15
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EP0733108A1 (en) 1996-09-25
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