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
- 来源:
- 关键词:
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
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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