NEW SIGNALING PATHWAY PROBES BASED ON NATURAL TOXINS

基于天然毒素的新信号通路探针

基本信息

  • 批准号:
    6019426
  • 负责人:
  • 金额:
    $ 20.91万
  • 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:
    1998-08-01 至 2002-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION: There is a structurally diverse group of natural toxins, includin okadaic acid, calyculin, microcystin LR, and tautomycin, that exert their cytotoxic effects by inhibiting the serine-threonine protein phosphatases PP1 and PP2A. This activity dramatically increases the phosphorylation state of a variety of proteins within the cell, a process that can have profound effects such as the disastrous disruption of intracellular signal trafficking, the deposition of proteinacious plaque and fibrils, and even unregulated cellular proliferation. The compounds themselves are therefore not only acute hepatotoxins, but also tumor promotors. Interestingly, despite the dissimilarities of the toxins structures, these compounds are competitive inhibitors, namely, their PP1/PP2A binding sites overlap. Because as a group they inhibit PP1 and PP2A quite potently and specifically relative to other known phosphatases such as PP2B (calcineurin), PP2C, and the tyrosine phosphatases, several members of this group have become important probes of intracellular signalling pathways. However, there are problems of poor selectivity between the two phosphatases, which can result in ambiguous results when attempts are being made to define the separate roles of PP1 and PP2A in a given process. In particular, there is no known membrane-permeable small molecule that inhibits PP1 with good selectivity. A recently published X-ray crystal structure of a PP1-microcystin LR complex provides a unique opportunity to explore binding interactions of all these inhibitors with both PP1 and PP2A, and to develop new selective inhibitors based on these natural products.
描述:有一组结构多样的天然毒素,

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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A RICHARD CHAMBERLIN其他文献

A RICHARD CHAMBERLIN的其他文献

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{{ truncateString('A RICHARD CHAMBERLIN', 18)}}的其他基金

TRIDENT
三叉戟
  • 批准号:
    6291662
  • 财政年份:
    2001
  • 资助金额:
    $ 20.91万
  • 项目类别:
NEW SIGNALING PATHWAY PROBES BASED ON NATURAL TOXINS
基于天然毒素的新信号通路探针
  • 批准号:
    6181136
  • 财政年份:
    1998
  • 资助金额:
    $ 20.91万
  • 项目类别:
NEW SIGNALING PATHWAY PROBES BASED ON NATURAL TOXINS
基于天然毒素的新信号通路探针
  • 批准号:
    2602736
  • 财政年份:
    1998
  • 资助金额:
    $ 20.91万
  • 项目类别:
Control of PP1/PP2A Activity With Small Molecule Toxins
用小分子毒素控制 PP1/PP2A 活性
  • 批准号:
    6871233
  • 财政年份:
    1998
  • 资助金额:
    $ 20.91万
  • 项目类别:
Control of PP1/PP2A Activity With Small Molecule Toxins
用小分子毒素控制 PP1/PP2A 活性
  • 批准号:
    7218074
  • 财政年份:
    1998
  • 资助金额:
    $ 20.91万
  • 项目类别:
NEW SIGNALING PATHWAY PROBES BASED ON NATURAL TOXINS
基于天然毒素的新信号通路探针
  • 批准号:
    6386897
  • 财政年份:
    1998
  • 资助金额:
    $ 20.91万
  • 项目类别:
Control of PP1/PP2A Activity With Small Molecule Toxins
用小分子毒素控制 PP1/PP2A 活性
  • 批准号:
    7030245
  • 财政年份:
    1998
  • 资助金额:
    $ 20.91万
  • 项目类别:
Control of PP1/PP2A Activity With Small Molecule Toxins
用小分子毒素控制 PP1/PP2A 活性
  • 批准号:
    6777786
  • 财政年份:
    1998
  • 资助金额:
    $ 20.91万
  • 项目类别:
ENANTIOSELECTIVE SYNTHESIS OF MYO-INOSITOL DERIVATIVES
肌醇衍生物的对映选择性合成
  • 批准号:
    3305688
  • 财政年份:
    1992
  • 资助金额:
    $ 20.91万
  • 项目类别:
INTRODUCTION OF NON-NATURAL AMINO ACIDS INTO PROTEINS
将非天然氨基酸引入蛋白质中
  • 批准号:
    3301523
  • 财政年份:
    1991
  • 资助金额:
    $ 20.91万
  • 项目类别:

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