KR920702409A - 새로운 결합을 갖는 올리고뉴클레오티드 유사체 - Google Patents

새로운 결합을 갖는 올리고뉴클레오티드 유사체

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Publication number
KR920702409A
KR920702409A KR1019920700954A KR920700954A KR920702409A KR 920702409 A KR920702409 A KR 920702409A KR 1019920700954 A KR1019920700954 A KR 1019920700954A KR 920700954 A KR920700954 A KR 920700954A KR 920702409 A KR920702409 A KR 920702409A
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KR
South Korea
Prior art keywords
bond
oligomer
independently
ycx
modified
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KR1019920700954A
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English (en)
Inventor
매튜시 마크
Original Assignee
원본미기재
길리드 사이언스 인코오퍼레이티드
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.)
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Priority claimed from US07/559,957 external-priority patent/US5264564A/en
Application filed by 원본미기재, 길리드 사이언스 인코오퍼레이티드 filed Critical 원본미기재
Publication of KR920702409A publication Critical patent/KR920702409A/ko

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity

Abstract

내용 없음

Description

새로운 결합을 갖는 올리고뉴클레오티드 유사체
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 DNA-이중결합에 대한 푸트 프린팅의 윤곽도, 이상적인 결과를 나타낸다.

Claims (13)

  1. 포스포디에스테르결합 또는 그들의 일반적인 치환체 결합인 각 뉴클레오티드 잔기 사이의 결합이 하나이상 구조식 -YCX2Y-로 치환되고 나머지는 그대로 포스포디에스테르결합 또는 그들의 일반적 치환체 결합으로 구성되는 변형을 하는 것을 특징으로 하는 생물학적 부위와 결합하는데 유용한 뉴클레오티드 서열을 포함하는 변형된 올리고머 또는 그들의 유도체, 여기에서 각 Y는 독립적으로 0 또는 S이고, 각 X는 독립적으로 선택되어지는 안정화시키는 치환체이다.
  2. 생물학적 부위를 결합시키는데 유용한 뉴클레오티드서열을 포함하는 것을 특징으로 하는 다음 구조식(Ⅰ)의 올리고머 또는 그들의 유도체.
    여기서 각 B는 독립적으로 퓨린 또는 피리미딘잔기이거나 여기서 정의한 바와 같은 유사잔기이고, Z는 독립적으로 여기서 정의한 바와 같은 포스포디에스테르의 일반적 치환체인 -P(O) -이거나 -CX2-이고; X는 독립적으로 안정화시키는 기이고, n은 1-200이고, 각 m은 0 또는 1이고, 그리고 최소한 한개의 Z는 CX2이고 각 Y는 독립적으로 O 또는 S이다.
  3. 제1항 또는 제2항에 있어서, 하나의 -YCX2Y-결합중에 포함된 두개의 X가 같거나 및/또는 최소한 두개의 결합이 상기 -YCX2Y-인 것을 특징으로하는 변형올리고머.
  4. 제3항에 있어서, 최소한 4개의 뉴클레오티드중 최소한 한부위에서 -YCX2Y-결합과 포스포디에스테르 타입 결합이 바꾸어지는 것을 특징으로 하는 변형올리고머.
  5. 제1항 내지 제4항중 어느 한항에 있어서, X가 H; 카복실 또는 그들의 에스테르 또는 아미드; -SOR 또는 -SO2R (여기서 R이 알킬(1-6C)이다); -CN; 및 -CF3로 구성되는 군에서 선택되어지거나; 또는 X가 -(CH2)nW [여기서 n은 1-3의 정수이고 W는 할로; 카복실 또는 그들의 에스테르 또는 아미드; 포스페이트 또는 포스포네이트 또는 그들의 에스테르; -SOR 또는 -SO2R,여시서 R은 알킬(1-6C)이다; -CN; -NO2; -CF3; -OH, -OR 및 1급, 2급 또는 3급아민]인 것을 특징으로 하는 변형올리고머.
  6. 제1항 내지 제4항중 어느 한항에 있어서, 각 X가 H인 것을 특징으로 하는 변형올리고머.
  7. 제5항에 있어서, 최소한 하나이상의 -YCX2Y-가 다음과 같은 것을 특징으로 하는 올리고머.
  8. 제1항 내지 제7항중 어느 한항에 있어서, 올리고머가 이량체 또는 3량체인 것을 특징으로 하는 올리고머.
  9. 제1항 내지 제8항중 어느 한항에 있어서, -P(O)O-에 대한 일반적인 치환체가 P(O)S, P(O)NR2, P(O)R, P(O)OR, CO 또는 CNR2(여기서 R은 H 또는 1-6C의 알킬이고 R'는 1-6C의 알킬이다)로 구성되는 군에서 선택되어지는 것을 특징으로 하는 올리고머.
  10. 제1항 내지 제9항중 어느 한항에 있어서, 유도체는 라벨, 삽입체 또는 약물과 포합체를 구성하는 것을 특징으로 하는 올리고머.
  11. 고체지지체에 부착된 식 1의 화합물(여기서, n=1-3이고 모든 Z가 CX2임)을 표준시약으로 처리하여 추가적인 뉴클레오티드와 포스포디에스테르결합을 형성하는 것으 이루어진 것을 특징으로 하는 식 -YCX2Y-의 결합이 적어도 하나 이상 함유되는 변형된 올리고뉴클오티드의 합성방법.
  12. 뉴클레오티드 또는 그외의 다른 생물학적 DNA-결합부위와 특이결합하여 그 부위를 불활성화시킬수 있는 청구항 1내지 10항의 변형올리고머의 유효량을 환자에게 투여하는 것을 특징으로 하는 상기 뉴클레오티드 또는 그외의 다른 생물학적 DNA-결합부위가 존재함으로써 일어나는 질병의 치료방법.
  13. 다음 구조식의 화합물,
    여기서 Y는 O 또는 S이고; B는 퓨린 또는 피리미딘 잔기 또는 여기서 정의한 바와같은 유사잔기이고; X'는 2개의 X'가 H일 수 없는 경우에는 독립적으로 안정기이고; R은 헤테로싸이클을 더 함유할 수 있는 방향족 또는 지방족 히드로카빌기이고; Pr 은 H 또는 보호기이다.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019920700954A 1989-10-24 1990-10-24 새로운 결합을 갖는 올리고뉴클레오티드 유사체 KR920702409A (ko)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US42628689A 1989-10-24 1989-10-24
US426286 1989-10-24
US44894189A 1989-12-11 1989-12-11
US448941 1989-12-11
US07/559,957 US5264564A (en) 1989-10-24 1990-07-30 Oligonucleotide analogs with novel linkages
US559957 1990-07-30
PCT/US1990/006110 WO1991006629A1 (en) 1989-10-24 1990-10-24 Oligonucleotide analogs with novel linkages

Publications (1)

Publication Number Publication Date
KR920702409A true KR920702409A (ko) 1992-09-04

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Country Status (8)

Country Link
EP (1) EP0498843B1 (ko)
JP (1) JPH05504553A (ko)
KR (1) KR920702409A (ko)
AT (1) ATE139255T1 (ko)
AU (1) AU653504B2 (ko)
CA (1) CA2071483C (ko)
DE (1) DE69027443T2 (ko)
WO (1) WO1991006629A1 (ko)

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AU6724590A (en) 1991-05-31
AU653504B2 (en) 1994-10-06
EP0498843B1 (en) 1996-06-12
JPH05504553A (ja) 1993-07-15
WO1991006629A1 (en) 1991-05-16
EP0498843A1 (en) 1992-08-19
DE69027443D1 (de) 1996-07-18
CA2071483A1 (en) 1991-04-25
CA2071483C (en) 2001-04-17
DE69027443T2 (de) 1998-03-19
ATE139255T1 (de) 1996-06-15
EP0498843A4 (en) 1992-11-04

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