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Boranophosphate DNA: RNA Hybrids as Probes of RNase H

Boranophosphate DNA: RNA Hybrids as Probes of RNase H
硼磷酸 DNA:作为 RNase H 探针的 RNA 杂交体
批准号:
6621811
负责人:
BARBARA RAMSAY SHAW
金额:
$30.11万
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
项目状态:
已结题
起止时间:
1998-05-01 至 2006-01-31

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中文摘要
翻译
描述(由申请人提供):硼代磷酸盐 (BH 3-ODN)是一类新的磷修饰的寡核苷酸, 在化学上与天然DNA不同,因为硼烷(BH-)基团取代了其中一个 磷酸二酯骨架中的非桥氧。BH 3-ODN更多 亲脂性和更耐核酸酶比天然DNA;他们形成 沃森-克里克双链体,并激活RNase H介导的切割 互补RNA硼磷酸盐加入天然磷酸二酯, (单-和二-)硫代酸酯,和更核酸酶敏感的2 '-F-阿拉伯糖核酸 酸,作为寡核苷酸的唯一类别, 通过酶协调RNA/寡核苷酸杂合体中的mRNA降解 核糖核酸酶H.尽管最近反义核酸的应用有所改进, 然而,在体内的寡核苷酸中,仍需要进一步的进展。的目标 本文的主要工作是:(1)合成一组硼磷酸寡核苷酸 和靶向ras基因的混合骨架嵌合体;(2)评估 BH_3--ODN和嵌合体激活Tnase H_1的潜力;(3)评估 BH 3--ODN的生物物理性质,包括热力学、结构和 它们与RNA寡核苷酸杂交的动力学,并研究 BH_3-ODN /RNA/RNase H复合物中RNA水解的动力学。(4)到 检查BH 3-ODN的渗透和在细胞中的定位,以及其他 药理学性质;和(5)探测序列和结构 通过我们的化学对RNase H特异性的要求。的 硼磷酸盐提供了一个新的平台,用于探测 结构和序列对RNase H催化作用。我们的总体目标是更好地 了解硼磷酸盐独特的化学和生物特性 寡核苷酸,并进一步了解RNase的作用机制 H和反义试剂。这些信息可以让我们设计出更有效的 用于治疗癌症和病毒性疾病的反义药物。
英文摘要
DESCRIPTION (provided by applicant): The oligonucleoside boranophosphates (BH3--ODN) are a new class of phosphorus modified oligonucleotides that differ chemically from natural DNA in that a borane (BH-) group replaces one of the non-bridging oxygens in the phosphodiester backbone. BH3--ODN are more lipophilic and much more resistant to nucleases than natural DNA; they form Watson-Crick duplexes, and activate the Rnase H-mediated cleavage of complementary RNA. The boranophosphates join the natural phosphodiester, the (mono-and di-) thioates, and the more-nuclease-susceptible 2'-F-arabinonucleic acids, as the only classes of oligonucleotides that by themselves can orchestrate mRNA degradation in RNA/oligonucleotide hybrids via the enzyme RNase H. Despite recent improvements in the utility of antisense oligonucleotides in vivo, further progress is still needed. The goals of the proposed work are: (1) To synthesize a set of borano phosphate oligonucleotides and mixed-backbone chimeras targeted against the ras gene; (2) To evaluate the potential of BH3--ODN and chimeras to activate Tnase H1; (3) To evaluate biophysical properties of BH3--ODN including the thermodynamics, structure, and kinetics of their hybridization with RNA oligonucleotides and to study the kinetics of hydrolysis of RNA in BH3--ODN /RNA/Rnase H complexes. (4) To examine penetration of BH3-ODN and localization in cells, and other pharmacological properties; and (5) to probe the sequence and structural requirements for Rnase H specificity through our chemistry. The boranophosphates provide a new platform for probing the subtle effects of structure and sequence on RNase H catalysis. Our overall goals are to better understand the unique chemical and biological properties of boranophosphate oligonucleotides and gain further insight into the mechanism of action of RNase H and antisense agents. This information should allow us to design more potent antisense drugs for treating cancer and viral diseases.
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Boronated L-nucleotides targeted against HIV
  • 批准号:
    6627841
  • 项目类别:
  • 资助金额:
    $30.8万
  • 财政年份:
    2002
  • 负责人:
    BARBARA RAMSAY SHAW
  • 依托单位:
Boronated L-nucleotides targeted against HIV
  • 批准号:
    6865421
  • 项目类别:
  • 资助金额:
    $30.8万
  • 财政年份:
    2002
  • 负责人:
    BARBARA RAMSAY SHAW
  • 依托单位:
Boronated L-nucleotides targeted against HIV
  • 批准号:
    6496596
  • 项目类别:
  • 资助金额:
    $30.8万
  • 财政年份:
    2002
  • 负责人:
    BARBARA RAMSAY SHAW
  • 依托单位:
Boronated L-nucleotides targeted against HIV
  • 批准号:
    6708840
  • 项目类别:
  • 资助金额:
    $30.8万
  • 财政年份:
    2002
  • 负责人:
    BARBARA RAMSAY SHAW
  • 依托单位:
海外基金