DESIGN AND SYNTHESIS OF NUCLEOTIDE ANALOGUES

核苷酸类似物的设计与合成

基本信息

  • 批准号:
    6269685
  • 负责人:
  • 金额:
    $ 21.36万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1998
  • 资助国家:
    美国
  • 起止时间:
    1998-02-01 至 1999-01-31
  • 项目状态:
    已结题

项目摘要

(Applicant's Description) An important goal of the program project is the development of a high sensitivity polymerase chain reaction/restriction endonuclease/ligase detection reaction (PCR/RE/LDR) method to identify specific mutations in the presence of excess normal DNA (Sensitivity of 1 in 100,000 - 1,000,000 cells). To this end, a new class of nucleotide analogues herein termed "convertides", have been designed to provide a means to convert a wild-type sequence into one which contains a restriction endonuclease recognition site. Convertides are defined as nucleoside analogues that have base modifications or replacements which allow them to pair to one or more of the natural bases in hybridization step ("read"), and also to function as a template for another base in a DNA replication reaction ("write"). A successful convertide will pair to one or more natural bases when annealing to a target, allowing for efficient extension by Tag polymerase (read), and also functions as a template for incorporation of another base the tag polymerase copies the primer-containing strand (write). For performing the 12 possible base conversions, 7 known deoxyribonucleoside analogues (Q1, Q2, Q4-Q8) and 13 newly-designed, modified deoxyribonucleosides (Q3, Q9-20) will be investigated. Specific objectives include: Synthetic routes to deoxyribonucleosides Q3, Q9-20 and their characterization. ([1] H and [13] C NMR, mass spectrometry, absorption spectroscopy, and elemental analysis; Synthesis of 5'- Dimethoxytrityl (DMT)-protected derivatives of the convertides will be prepared and transformed to 3'-phophoramidites and 3'-linked CPG solid supports for incorporation into oligonucleotides for Projects 1 and 3. The effect of the modified nucleotides on duplex structure will be determined by measuring and analyzing the helix-coil transition of sets of duplexes containing each of the Q nucleosides opposite each of the natural nucleosides. Synthesis of primers with backbone (phosphate and sugar) modifications at or near the 3'-end will be explored for: (1) preventing cleavage of 3'-convertide by proofreading polymerases in PCR reactions (Project 1) and (2) improving fidelity of ligase reactions by destabilization of ligase-DNA complex (Project 3).
(申请人描述)本项目的一个重要目标是

项目成果

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Donald E. BERGSTROM其他文献

Donald E. BERGSTROM的其他文献

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{{ truncateString('Donald E. BERGSTROM', 18)}}的其他基金

Drug Delivery DDMS Program Leaders
药物输送 DDMS 项目负责人
  • 批准号:
    8182760
  • 财政年份:
    2010
  • 资助金额:
    $ 21.36万
  • 项目类别:
Program Leaders
项目负责人
  • 批准号:
    8182734
  • 财政年份:
    2010
  • 资助金额:
    $ 21.36万
  • 项目类别:
DESIGN AND SYNTHESIS OF NUCLEOTIDE ANALOGUES
核苷酸类似物的设计与合成
  • 批准号:
    6300471
  • 财政年份:
    2000
  • 资助金额:
    $ 21.36万
  • 项目类别:
DESIGN AND SYNTHESIS OF NUCLEOTIDE ANALOGUES
核苷酸类似物的设计与合成
  • 批准号:
    6103021
  • 财政年份:
    1999
  • 资助金额:
    $ 21.36万
  • 项目类别:
DESIGN AND SYNTHESIS OF NUCLEOTIDE ANALOGUES
核苷酸类似物的设计与合成
  • 批准号:
    6237514
  • 财政年份:
    1997
  • 资助金额:
    $ 21.36万
  • 项目类别:
MODIFIED NUCLEOSIDES AS TOOLS FOR MOLECULAR BIOLOGY
修饰核苷作为分子生物学的工具
  • 批准号:
    6180751
  • 财政年份:
    1996
  • 资助金额:
    $ 21.36万
  • 项目类别:
MODIFIED NUCLEOSIDES AS TOOLS FOR MOLECULAR BIOLOGY
修饰核苷作为分子生物学的工具
  • 批准号:
    2685067
  • 财政年份:
    1996
  • 资助金额:
    $ 21.36万
  • 项目类别:
MODIFIED NUCLEOSIDES AS TOOLS FOR MOLECULAR BIOLOGY
修饰核苷作为分子生物学的工具
  • 批准号:
    2192442
  • 财政年份:
    1996
  • 资助金额:
    $ 21.36万
  • 项目类别:
MODIFIED NUCLEOSIDES AS TOOLS FOR MOLECULAR BIOLOGY
修饰核苷作为分子生物学的工具
  • 批准号:
    2392246
  • 财政年份:
    1996
  • 资助金额:
    $ 21.36万
  • 项目类别:
MODIFIED NUCLEOSIDES AS TOOLS FOR MOLECULAR BIOLOGY
修饰核苷作为分子生物学的工具
  • 批准号:
    6386205
  • 财政年份:
    1996
  • 资助金额:
    $ 21.36万
  • 项目类别:

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  • 批准号:
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