KR940703846A - 갭(gap)이 형성된 2′ 변성된 올리고뉴클레오티드(gapped 2′ modifed oligonucleotides) - Google Patents

갭(gap)이 형성된 2′ 변성된 올리고뉴클레오티드(gapped 2′ modifed oligonucleotides)

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KR940703846A
KR940703846A KR1019940702197A KR19940702197A KR940703846A KR 940703846 A KR940703846 A KR 940703846A KR 1019940702197 A KR1019940702197 A KR 1019940702197A KR 19940702197 A KR19940702197 A KR 19940702197A KR 940703846 A KR940703846 A KR 940703846A
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bond
nucleoside
phosphorus
bound
nucleotide
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댄 쿡 필립
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비. 린네 파샬
아이시스 파마큐터컬즈 인코포레이티드
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Abstract

증가된 뉴클레아제 내성, 상보 스트랜드에 대한 결합친화도를 증가시키기 위한 치환그룹, 및 PNase H 효소를 활성화시키는 2＇-디옥시-에리트로-펜토푸라노실 뉴클레오티드의 하부염기서열을 갖는 올리고뉴클레오티드와 거대분자에 관한 것이다. 이러한 올리고 뉴클레오티드 및 거대분자는 진단과 연구목적을 위하여, 유기체내 단백질조절을 위하여, 그리고 안티센스 치료에 민감한 다른 조건의 처리, 탐지, 진단을 위하여 유용하다.

Description

갭(GAP)이 형성된 2＇ 변성된 올리고뉴클레오티드(GAPPED 2＇MODIFED OLIGONUCLEOTIDES)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 본 발명의 올리고뉴클레오시드와 참고화합물이 용량반응 활성을 나타낸 그래프, 제2도는 본 발명의 올리고뉴클레오시드와 참고화합물의 용량반응 활성을 나탄낸 막대그래프.

Claims (48)

  1. 헥산의 스트랜드에 특정적으로 잡종화 할수 있는 뉴클레오티드 단위의 염기서열로 조성되는 올리고뉴클레오티드에 있어서, 상기 뉴클레오티드 단위중 적어도 하나는 상기 올리고뉴클레오티드의 뉴클레오티드아제 내성을 증가시키도록 작용하고; 상기 뉴클레오티드 단위중 적어도 하나는 헥산의 상기 스트랜드에 상기 올리고뉴클레오티드의 결합 친화도를 증가시키는 치환그룹을 함유하며; 그리고 다수의 상기 뉴클레오티드 단위는 2＇-디옥시-에리트로 펜토푸라노실 당 성분을 함유하는데, 상기 2′-디옥시-에리트로 펜토푸라노실 뉴클레오티드 단위는 연속적으로 뉴클레오티드 단위의 상기 염기서열내에 위치하는 것으로 조성되는 것을 특징으로 하는 올리고뉴클레오티드.
  2. 제1항에 있어서, 결합친화도를 증가시키는 상기 치환그룹이 2＇-치환그룹으로 조성되는 것을 특징으로 하는 올리고뉴클레오티드.
  3. 제2항에 있어서, 상기 2′-치환그룹이 플루오로, C1-C9 알콕시, C1-C9 아미노 알콕시, 알릴옥시, 이미다졸알콕시 및 폴리(에틸렌 글리콜)인 것을 특징으로 하는 올리고뉴클레오티드.
  4. 제1항에 있어서, 상기 각 뉴클레오티드 단위는 포스포로티오에이트 또는 포스포로디티오에이트 뉴클레오티드인 것을 특징으로 하는 올리고뉴클레오티드.
  5. 제1항에 있어서, 상기 올리고뉴클레오티드의 3＇말단 뉴클레오티드 단위는 상기 뉴클레오티드 단위의 2＇또는 3＇위치중 적어도 하나의 위치에 뉴클레아제 내성변성 그룹을 함유하는 것을 특징으로 하는 올리고뉴클레오티드.
  6. 제1항에 있어서, 다수의 상기 뉴클레오티드 단위는 상기 핵산의 스트랜드에 상기 올리고뉴클레오티드의 결합 친화도를 증가시키는 치환 그룹을 함유하는데, 상기 치환체 함유 뉴클레오티드는 제1뉴클레오티드 단위 하부-염기서열 및 제2뉴클레오티드단위 하부-염기서열로 나뉘어지고; 그리고 상기 다수의 2＇-디옥시-에리트로-펜토푸라노실 뉴클레오티드 단위는 상기 제1뉴클레오티드 단위 하부-염기서열과 상기 제2뉴클레오티드 단위 하부-염기서열 사이의 뉴클레오티드 단위의 상기 염기서열내에 위치하는 것을 특징으로 하는 올리고뉴클레오티드.
  7. 제1항에 있어서, 다수의 상기 뉴클레오티드 단위는 핵산의 상기 상보스트랜드에 상기 올리고뉴클레오티드의 결합 친화도를 증가시키는 치환그룹을 함유하며; 그리고 상기 치환체-함유 뉴클레오티드의 최소한 한 부분은 상기 올리고뉴클레오티드의 3＇말단 또는 5＇말단의 어느 하나에 연속적으로 위치하는 것을 특징으로 하는 올리고뉴클레오티드.
  8. 제1항에 있어서, 상기 뉴클레오티드 단위의 적어도 5개는 2＇-디옥시-에리트로-펜토푸라노실 당성분을 갖는데, 상기 최소한 5개의 2＇-디옥시-에리트로-펜토푸라노실 뉴클레오티드 단위는 연속적으로 뉴클레오티드의 상기 염기서열내에 위치하는 것을 특징으로 하는 올리고뉴클레오티드.
  9. 제1항에 있어서, 상기 뉴클레오티드 단위의 약 1 내지 8개는 상기 상보 스트랜드에 상기 올리고뉴클레오티드의 결합친화도를 증가시키는 치환그룹을 함유하는데, 상기 치환체-함유 뉴클레오티드 단위는 연속적으로 뉴클레오티드 단위의 상기 염기서열내에 위치하는 것을 특징으로 하는 올리고뉴클레오티드.
  10. 제1항에 있어서, 상기 뉴클레오티드 단위의 약 1 내지 8개는 상기 상보 스트랜드에 상기 올리고뉴클레오티드의 결합친화도를 증가시키는 치환그룹을 함유하는데, 상기 치환체-함유 뉴클레오티드 단위는 연속적으로 뉴클레오티드 단위의 상기 염기서열내에 위치하며; 그리고 상기 뉴클레오티드 단위의 최소한 5개는 2＇-디옥시-에리트로-펜타푸라노실 뉴클레오티드 단위는 연속적으로 뉴클레오티드 단위의 상기 염기서열내에 위치하는 것을 특징으로 하는 올리고뉴클레오티드.
  11. 핵산의 스트랜드에 특정적으로 잡종화 할 수 있는 포스포로티오에이트 뉴클레오티드의 염기서열로 조성되는 올리고뉴클레오티드에 있어서, 다수의 상기 뉴클레오티드는 핵산의 상기 스트랜드에 상기 올리고뉴클레오티드의 결합친화도를 증가시키는 치환그룹을 함유하며; 그리고 다수의 상기 뉴클레오티드는 2＇-디옥시-에리트로-펜토푸라노실 당 성분을 갖는 것으로 조성되는 것을 특징으로 하는 올리고뉴클레오티드.
  12. 제11항에 있어서, 결합친화도를 증가시키는 상기 치환 그룹이 2＇-치환 그룹으로 조성되는 것을 특징으로 하는 올리고뉴클레오티드.
  13. 제12항에 있어서, 상기 2＇치환 그룹이 플루오로, C1-C9 알콕시, C1-C9 아미노알콕시 또는 알릴 옥시인 것을 특징으로 하는 올리고뉴클레오티드.
  14. 제12항에 있어서, 또한 2＇치환 그룹을 함유하는 다수의 상기 뉴클레오티드; 상기 2＇디옥시-에리트로-펜토푸라노실 뉴클레오티드는 상기 올리고뉴클레오티드내에 이들 위에 위치한 상기 2＇치환 그룹을 함유하는 뉴클레오티드의 그룹 사이에 위치하는 것을 포함하는 것을 특징으로 하는 올리고뉴클레오티드.
  15. 제11항에 있어서, 상기 치환체-함유 뉴클레오티드는 상기 올리고뉴클레오티드의 3＇말단 또는 5＇말단의 어느 하나에 위치하는 것을 특징으로 하는 올리고뉴클레오티드.
  16. 헥산의 스트랜드에 특정적으로 잡종화할 수 있는 포스포로티오에이트 뉴클레오티드의 염기서열로 조정되는 올리고뉴클레오티드에 있어서, 상기 뉴클레오티드의 제1부분이 2＇-디옥시-2＇-플루오로, 2＇-메톡시, 2＇-에톡시, 2＇-프로폭시, 2＇-아미노프로폭시 또는 2＇-알릴옥시 펜토푸라노실 당 성분을 가지며; 그리고 상기 뉴클레오티드의 또 다른 부분은 2＇-디옥시-에리트로-펜토푸라노실 당 성분을 갖는 것으로 조성되는 것을 특징으로 하는 올리고뉴클레오티드.
  17. 제16항에 있어서, 상기 뉴클레오티드의 상기 제1부분이 상기 올리고뉴클레오티드의 3＇ 말단 또는 5＇말단에 위치하는 것을 특징으로 하는 올리고뉴클레오티드.
  18. 제17항에 있어서, 상기 뉴클레오티드의 부가적인 부분이 2＇-디옥시-2＇-플로오르, 2＇메톡시, 2＇-에톡시, 2＇-프로폭시, 2＇-아미노프로폭시 또는 2＇-알릴옥시펜토푸라노실 당 성분을 가지며; 그리고 상기 뉴클레오티드의 또 다른 부분이 상기 올리고뉴클레오티드내 뉴클레오티드의 상기 제1부분과 상기 뉴클레오티드의 상기 부가적인 부분 사이에 위치하는 것을 포함하는 것을 특징으로 하는 올리고뉴클레오티드.
  19. 적어도 뉴클레오티드 중의 하나가 올리고뉴클레오티드의 내성을 증가시키며, 다수의 뉴클레오티드는 핵산의 스트랜드에 올리고뉴클레오티드의 결합친화도를 증가시키도록 그 위에 위치한 치환그룹을 가지며, 그리고 다수의 뉴클레오티드는 2＇-디옥시-에리트로-펜타루라노실 당 성분을 가지며, 단백질에 대한 코드화한 핵산의 스트랜드에 특정적으로 잡종화할 수 있는 뉴클레오티드의 염기서열을 갖는 올리고뉴클레오티드와 유기체를 접촉하는 것으로 조성되는 단백질의 바람직하지 않은 생성물에 의해 특징되는 질병을 갖는 유기체를 처치하는 방법.
  20. 제19항에 있어서, 각 상기 뉴클레오티드가 포스포로티오에이트 뉴클레오티드인 것을 특징으로 하는 방법.
  21. 제19항에 있어서, 상기 치환그룹이 2＇-치환 그룹인 것을 특징으로 하는 방법.
  22. 제21항에 있어서, 상기 2＇-치환 그룹이 플루오로, 알콕시, 아미노알콕시 또는 알릴 옥시인 것을 특징으로 하는 방법.
  23. 핵산의 스트랜드에 특정적으로 잡종화할 수 있는 뉴클레오티드의 염기서열을 갖는 올리고뉴클레오티드의 약제학적으로 효과적인 양, 올리고뉴클레오티드의 뉴클레아제 내성을 증가시키는 기능을 하는 뉴클레오티드중의 적어도 하나, 핵산의 상보 스트랜드에 올리고뉴클레오티드의 결합친화도를 증가시키도록 그 위에 위치한 치환 그룹을 갖는 다수의 뉴클레오티드, 2＇-디옥시-에리트로, 펜토푸라노실 당 성분을 갖는 다수의 뉴클레오티드; 및 약제학적으로 수용가능한 희석액 또는 담체로 조정되는 것을 특징으로 하는 약제학적 조성물.
  24. 핵산의 스트랜드에 특정적으로 잡종화할 수 있는 뉴클레오티드의 염기서열을 갖는 올리고뉴클레오티드와 상기 핵산 및 RNase H를 함유하는 시험용액을 접촉하는 것으로 조성되는, 여기서 뉴클레오티드중의 적어도 하나는 뉴클레아제 내성을 증가시키는 기능을 하며, 다수의 뉴클레오티드는 핵산의 상보 스트랜드에 올리고뉴클레오티드의 결합친화도를 증가시키도록 그 위에 위치한 치환그룹을 가지며, 그리고 다수의 뉴클레오티드는 2＇-디옥시-에리트로-펜토푸라노실 당 성분을 갖는, 시험관내 염기서열-특정 핵산을 변성시키는 방법.
  25. 핵산의 상보 스트랜드에 특정적으로 잡종화할 수 있는 뉴클레오티드의 염기서열을 갖는 올리고뉴클레오티드와 유기체를 접촉하여 조성되는, 여기서 뉴클레오티드중의 적어도 하나는 뉴클레아제 내성을 증가시키는 기능을 하며, 다수의 뉴클레오티드는 핵산의 상보 스트랜드에 올리고뉴클레오티드의 결합친화도를 증가시키도록 그 위에 위치한 치환그룹을 가지며, 그리고 다수의 뉴클레오티드는 2＇-디옥시-에리트로-펜토푸라노실 당 성분을 갖는, 유기체내 RNase H 및 잡종화를 동시에 증가시키는 방법.
  26. 상보 핵산에 잡종화되는 염기서열내 공유결합으로 결합된 다수의 뉴클레오티드로 조성되는 거대분자에 있어서, 상기 뉴클레오티드는 α-뉴클레오시드, 2＇-디옥시-에리트로-펜토푸라노실 β-뉴클레오시드를 함유하는 β-뉴클레오시드, 4＇-티오뉴클레오시드 및 탄소고리-뉴클레오시드로부터 선택되고; 상기 결합은 하전된 포스포러스 결합, 중성 포스포러스 결합 또는 비-포스포러스 결합으로부터 선택되며; 그리고 적어도 두 개의 뉴클레오시드 구역을 포함하는 결합 뉴클레오시드의 상기 염기서열에 있어서, 상기 구역의 제1은 하전되고 중성의 3＇-5＇ 포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 하전되고, 중성의 3＇-5＇ 포스포러스 결합에 의하여 결합된 상기 4＇-티오뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 4＇-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 4＇-티오뉴클레오시드, 포스포러스 결합에 의하여 결합된 상기 탄소고리-뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 상기 탄소고리-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 상기 탄소고리-뉴클레오시드, 하전되고, 중성의 2＇-5＇ 포스포러스 결합에 의하여 상기 β-뉴클레오시드, 및 비-포스포러스 결합에 의하여 결합된 β-뉴클레오시드로부터 선택된 뉴클레오시드를 포함하고; 그리고 상기 구역의 제2구역은 생리적 pH에서 음전하를 갖는 하전된 3＇-5＇ 포스포러스 결합에 의하여 결합된 상기 2＇-디옥시-에리트로-펜토푸라노실 β-뉴클레오시드를 포함하는 것으로 조성되는 것을 특징으로 하는 거대분자.
  27. 제26항에 있어서, 상기 제2구역은 상기 2＇-디옥시-에리트로-펜토푸라노실 β-뉴클레오시드를 적어도 3개 포함하는 것을 특징으로 하는 거대분자.
  28. 제26항에 있어서, 상기 제2뉴클레오시드 구역은 상기 제1뉴클레오시드 구역과 제3뉴클레오시드 구역 사이에 구역 사이에 위치하는데, 상기 제3뉴클레오시드 구역은 하전되고 중성의 3＇-5＇ 포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 하전되고 중성의 2＇-5＇포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 하전되고 중성의 3＇-5＇포스퍼스 결합에 의하여 결합된 상기 4＇-티오뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 4＇-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 4＇-티오뉴클레오시드, 포스포러스 결합에 의하여 결합된 상기 탄소고리-뉴클레오시드, 하전되고 중성의 2＇-5＇포스포러스 결합에 의하여 상기 탄소고리-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 상기 탄소고리-뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 상기 β-뉴클레오시드, 및 비-포스포러스 결합에 의하여 결합된 β-뉴클레오시드로부터 선택된 뉴클레오시드를 포함하는 것을 특징으로 하는 거대분자.
  29. 제26항에 있어서, 하전된 포스포러스 결합은 포스포디에스테르, 포스포로티오에이트, 포스포로디티오에이트, 포스포로셀레네이트 또는 포스포러디셀레네이트 결합을 포함하는 것을 특징으로 하는 거대분자.
  30. 제26항에 있어서, 하전된 포스포러스 결합이 포스포디에스테르 또는 포스포로티오에이트인 것을 특징으로 하는 거대분자.
  31. 제26항에 있어서, 상기 천연-포스포러스 결합은 알킬 및 아릴 포스포네이트, 알킬 및 아릴 포스포네이트, 알킬 및 아릴포스포로아미드트, 알킬 및 아릴 포스포로트리에스테르, 히드로젠 포스포네이트 및 보라노포스페이트 결합을 포함하는 것을 특징으로 하는 거대분자.
  32. 제26항에 있어서, 상기 비-포스포러스 결합은 펩티드 결합, 히드라진 결함, 히드록시-아민 결합, 카바메이트 결합, 몰포린 결합, 카르보네이트 결합, 아미드 결합, 옥시메틸렌이민 결합, 카르보에니트 결합, 아미드 결합, 옥시메틸렌이민 결합, 히드라지드 결합, 실릴 결합, 술파이드 결합 디술파이드 결합, 디술파이드 결합, 술폰 결합, 술폭사이드 결합, 술폰네이트 결합, 술폰아미드 결합, 포름아세탈 결합 티오포름아세탈 결합, 옥실 결합, 및 에틸렌 글리콜 결합을 포함하는 것을 특징으로 하는 거대분자.
  33. 제26항에 있어서, 상기 제1뉴클레오시드 구역은 하전된 또는 중성의 3＇5＇포스포러스 결합에 의하여 결합된 적어도 두 개의 α-뉴클레오시드를 포함하는 것을 특징으로 하는 거대분자.
  34. 상보 핵산에 잡종화되는 염기서열내 공유결합으로 결합된 다수의 단위로 조성되는 거대분자에 있어서, 상기 단위는 뉴클레오시드 및 핵염기로부터 선택되고; 상기 뉴클레오시드는 α-뉴클레오시드, 2＇-디옥시-에리트로-펜토푸라노실 β-뉴클레오시드를 함유하는 β-뉴클레오시드, 4＇-티오뉴클레오시드 및 탄소고리-뉴클레오시드로부터 선택되고; 상기 핵염기는 퓨린-9-일 및 피리미딘-1-일 헤테로 고리 염기로부터 선택되고; 상기 결합은 하전된 3＇-5＇포스포러스, 중성 3＇-5＇-포스포러스, 하전된 2＇-5＇ 포스포러스, 중성 2＇-5＇ 포스포러스 또는 비-포스포러스 결합으로 선택되고 ; 그리고 결합된 단위의 상기 염기서열은 적어도 두 구역으로 나뉘어지는데, 상기 제1구역은 비-포스포러스 결합에 의하여 결합된 상기 핵염기 및 비-당 속박그룹을 경유한 포스페이트 결합에 연결된 핵염기, 및 상기 구역의 제1구역은 하전되고 중성의 3＇-5＇ 포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 하전되고, 중성의 3＇-5＇ 포스포러스 결합에 의하여 결합된 상기 4＇-티오뉴클레오시드, 하전되고 중성의 2＇-2＇ 포스포러스 결합에 의하여 4＇-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 4＇-티오뉴클레오시드, 포스포러스 결합에 의하여 결합된 상기 탄소고리-뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 상기 탄소고리-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 상기 탄소고리-뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 상기 β-뉴클레오시드, 및 비-포스포러스 결합에 의하여 결합된 β-뉴클레오시드로부터 선택된 뉴클레오시드로부터 선택된 뉴클레오시드를 포함하고; 그리고 상기 제2구역은 생리적 pH에서 음전하를 갖는 하전된 3＇-5＇ 포스포러스 결합에 의하여 결합된 상기 2＇-디옥시-에리트로-펜토푸라노실 β-뉴클레오시드를 포함하는 것으로 조성되는 것을 특징으로 하는 거대분자.
  35. 제34항에 있어서, 상기 제1구역은 비-포스페이트 결합에 의하여 결합된 적어도 2개의 핵염기를 포함하는 것을 특징으로 하는 거대분자.
  36. 제35항에 있어서, 상기 포스페이트 결합은 펩티드 결합인 것을 특징으로 하는 거대분자.
  37. 제35항에 있어서, 상기 제2구역은 상기 제1구역과 제3구역 사이에 위치하는데, 상기 제3구역은 비-포스포러스 결합에 의하여 결합된 상기 핵염기 및 비-당속박그룹을 경유한 포스페이트 결합에 연결된 핵염기, 및 상기 구역의 제1구역은 하전되고 중성의 3＇-5＇ 포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 하전되고, 중성의 2＇-5＇ 포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 상기α-뉴클레오시드, 하전되고 중성의 3＇-5＇ 포스포러스 결합에 의하여 결합된 상기 4＇-티오뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 4＇-뉴클레오시드, 비-포스포러스 결합에 의하여 결랍된 4＇-티오뉴클레오시드, 포스포러스 결합에 의하여 결합된 상기 탄소고리-뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 상기 탄소고리-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 상기 탄소고리-뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 상기 β-뉴클레오시드, 및 비-포스포러스 결합에 의하여 결합된 β-뉴클레오시드로부터 선택된 뉴클레오시드를 포함하는 것을 특징으로 하는 거대분자.
  38. 제35항에 있어서, 상기 핵염기는 아데닌, 구아닌, 시토신, 우라실, 티민, 크산틴, 하이포크산틴, 2-아미노아데닌, 6-메틸 및 다른 알킬 아데닐, 2-프로필 및 다른 알킬 아데닌, 5-할로 우라실 및 시토신, 6-아조 우라실, 시토신 및 티민, 5-우라실(슈도 우라실), 4-티오우라실, 8-할로, 아미노, 티올, 티올알킬, 히드록실 및 8-치환 아데닌 및 구아닌, 또는 5-트리플루오로 메틸 우라실 및 시토신으로부터 선택되는 것을 특징으로 하는 거대분자.
  39. 상보 헥산에 잡종화되는 염기서열내 공유결합으로 결합된 다수의 단위로 조성되는 거대분자에 있어서, 상기 단위는 뉴클레오시드 및 핵염기로부터 선택되고; 상기 뉴클레오시드는 α-뉴클레오시드, β-뉴클레오시드, 4＇-티오뉴클레오시드 및 탄소고리-뉴클레오시드로부터 선택되고; 상기 핵 염기는 퓨린-9-일 및 피리미딘-1-일 헤테로고리 염기로부터 선택되고; 상기 결합은 하전된 포스포러스, 중성 포스포러스 또는 비-포스포러스 결합으로부터 선택되며; 그리고 결합된 단위의 상기 염기서열은 적어도 두 구역을 나뉘어지는데, 상기 구역의 제1구역은 하전되고 중성의 3＇-5＇ 포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 상기 α-뉴클레오시드, 하전되고 중성의 3＇-5＇ 포스포러스 결합에 의하여 결합된 상기 4＇-티오뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 4＇-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 4＇티오뉴클레오시드, 포스포러스 결합에 의하여 결합된 상기 탄소고리-뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 상기 탄소고리-뉴클레오시드, 비-포스포러스 결합에 의하여 결합된 상기 탄소고리-뉴클레오시드, 하전되고 중성의 2＇-5＇ 포스포러스 결합에 의하여 상기 β-뉴클레오시드, 및 비-포스포러스 결합에 의하여 결합된 β-뉴클레오시드로부터 선택된 뉴클레오시드를 포함하고; 그리고 상기 구역의 제2구역은 비-당 속박 성분을 경유하여 포스페이트 결합에 연결된 핵 염기 및 비-포스포러스 결합에 의하여 결합된 상기 핵염기를 함유하는 것으로 조성되는 것을 특징으로 하는 거대분자.
  40. 제38항에 있어서, 상기 비-포스페이트 결합이 펩티드 결합인 것을 특징으로 하는 거대분자.
  41. 제38항에 있어서, 다수의 상기 제1구역을 포함하는 것을 특징으로 하는 거대분자.
  42. 제38항에 있어서, 다수의 제1구역을 포함하는 것을 특징으로 하는 거대분자.
  43. 제41항에 있어서, 다수의 상기 제1구역을 포함하는 것을 특징으로 하는 거대분자.
  44. 유기체와 제34항의 화합물과 접촉하는 것으로 조성되는 단백질의 바람직하지 않은 생성물로 특징되는 질병을 갖는 유기체를 처치하는 방법.
  45. 약제학적으로 수용가능한 희석제 또는 담체 및 제34항의 화합물의 약제학적으로 효과적인 양으로 조성되는 약제학적 조성물.
  46. RNase H 및 핵산을 함유하는 시험용액을 제34항의 화합물과 접촉시키는 것으로 조성되는, 염기서열-특정핵산을 시험관내에 변성시키는 방법.
  47. 유기체와 제39항의 화합물을 접촉시키는 것으로 조성되는 단백질의 바람직하지 않은 생성물에 의해 특정되는 질병을 갖는 유기체를 처치하는 방법.
  48. 약제학적으로 수용가능한 희석액 또는 담체 및 제39항의 화합물의 약제학적으로 효과적인 양으로 조성되는 약제학적 조성물.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019940702197A 1991-12-24 1992-12-23 갭(gap)이 형성된 2′ 변성된 올리고뉴클레오티드(gapped 2′ modifed oligonucleotides) KR940703846A (ko)

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US81496191A 1991-12-24 1991-12-24
US814,961 1991-12-24
PCT/US1992/011339 WO1993013121A1 (en) 1991-12-24 1992-12-23 Gapped 2' modified oligonucleotides

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EP1695979B1 (en) 2011-07-06
EP0618925A4 (en) 1997-01-02
CA2126691C (en) 2003-05-06
EP1044987B1 (en) 2006-02-15
DE69232032T2 (de) 2002-06-06
ATE515510T1 (de) 2011-07-15
US20020160379A1 (en) 2002-10-31
ATE204879T1 (de) 2001-09-15
EP0618925A1 (en) 1994-10-12
ATE317848T1 (de) 2006-03-15
EP1044987A2 (en) 2000-10-18
JP3131222B2 (ja) 2001-01-31
DK0618925T3 (da) 2001-11-12
DK0618925T4 (da) 2012-07-09
EP0618925B2 (en) 2012-04-18
JPH06511155A (ja) 1994-12-15
CA2126691A1 (en) 1993-07-08
US20050112563A9 (en) 2005-05-26
EP1695979A3 (en) 2006-09-06
EP1695979A2 (en) 2006-08-30
EP0618925B1 (en) 2001-08-29
US6326199B1 (en) 2001-12-04
US6146829A (en) 2000-11-14
DE69232032D1 (de) 2001-10-04
DK1695979T3 (da) 2011-10-10
DE69232032T3 (de) 2012-09-13
AU3427593A (en) 1993-07-28
DE69233599T2 (de) 2006-12-14
EP1044987A3 (en) 2001-10-04
WO1993013121A1 (en) 1993-07-08
US20040038274A1 (en) 2004-02-26
JP2001002696A (ja) 2001-01-09
AU669353B2 (en) 1996-06-06
DE69233599D1 (de) 2006-04-20

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