INTERACTIONS OF A NOVEL LIGAND WITH A MODEL CHANNEL
新型配体与模型通道的相互作用
基本信息
- 批准号:2023505
- 负责人:
- 金额:$ 10.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-05-01 至 2002-04-30
- 项目状态:已结题
- 来源:
- 关键词:Gastropoda Torpedo acetylcholine animal tissue chemical binding chemical models chemical synthesis crosslink fish electric organ high performance liquid chromatography ligands lipid bilayer membrane membrane channels membrane proteins membrane structure method development neurotoxins nicotinic receptors nuclear magnetic resonance spectroscopy protein structure radiotracer receptor binding
项目摘要
Membrane associated receptors and ion channels serve as the molecular basis
for electrical signaling, selective information transfer between excitable
cells, and controlling the activity of the nervous system. Contrary to
their biological significance, very little is known about how these
proteins recognize neurotransmitters and ligands at the molecular level.
The PI is interested in developing a novel methodology for revealing
molecular features governing ligand-receptor recognition using modern high-
field NMR spectroscopy. The methodology focuses on 1) designing relatively
small model systems for ligand-receptor complexes, 2) developing a chemical
strategy for synthesizing such models in the case of ion channels, the
ability to transport ions is retained, and 3) applying both solution and
solid-state NMR techniques to free ligands in aqueous solution, model
channels in detergent micelles, and ligand-receptor complexes in lipids.
Conotoxins, peptide neurotoxins from Conus snails, are ideal molecules for
providing a model system for studying ligand-receptor interactions. They
bind these membrane proteins with dissociation constants in nanomolar
range, and there are potentially tens of thousands of these peptide
ligands. The proposed project is based on exploiting their extraordinary
specificity in developing model systems suitable for structural studies by
NMR methods.
A novel ligand (psi-conotoxin), which is a non-competitive inhibitor of the
nicotinic acetylcholine receptor, has been recently discovered by the PI.
The present experimental evidence strongly suggests that the binding region
is at the carboxyl ends of the second transmembrane domains (M2). Such
model channel has been chemically synthesized, and structure determination
of the channel and its ligand bound complex will be the main focus of this
proposal. Successful execution of the research will provide leads for
rational drug design as well as for engineering subtype specific ligands
targeted to specific receptors and ion channels.
膜相关受体和离子通道作为分子基础
对于电信号传导,兴奋剂之间的选择性信息传递
细胞,并控制神经系统的活动。 与此相反
它们的生物学意义,人们对它们如何发挥作用知之甚少
蛋白质在分子水平上识别神经递质和配体。
PI 有兴趣开发一种新颖的方法来揭示
使用现代高科技控制配体受体识别的分子特征
场核磁共振波谱。 该方法侧重于 1)相对设计
配体-受体复合物的小型模型系统,2) 开发化学物质
在离子通道的情况下合成此类模型的策略,
保留了传输离子的能力,并且 3) 同时应用溶液和
固态核磁共振技术在水溶液中释放配体,模型
洗涤剂胶束中的通道和脂质中的配体-受体复合物。
芋螺毒素是来自芋螺的肽神经毒素,是理想的分子
提供研究配体-受体相互作用的模型系统。 他们
以纳摩尔解离常数结合这些膜蛋白
范围,并且可能有数万个这样的肽
配体。 拟议的项目是基于开发他们非凡的
开发适合结构研究的模型系统的特异性
核磁共振方法。
一种新型配体(psi-芋螺毒素),它是一种非竞争性抑制剂
PI最近发现了烟碱乙酰胆碱受体。
目前的实验证据强烈表明结合区域
位于第二跨膜结构域(M2)的羧基端。 这样的
模型通道已化学合成,并进行结构测定
通道及其配体结合复合物的研究将是本次研究的主要焦点
提议。 该研究的成功执行将为以下方面提供线索:
合理的药物设计以及工程亚型特异性配体
针对特定受体和离子通道。
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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{{ truncateString('KI-JOON SHON', 18)}}的其他基金
INTERACTIONS OF A NOVEL LIGAND WITH A MODEL CHANNEL
新型配体与模型通道的相互作用
- 批准号:
6386549 - 财政年份:1997
- 资助金额:
$ 10.36万 - 项目类别:
INTERACTIONS OF A NOVEL LIGAND WITH A MODEL CHANNEL
新型配体与模型通道的相互作用
- 批准号:
6181124 - 财政年份:1997
- 资助金额:
$ 10.36万 - 项目类别:
INTERACTIONS OF A NOVEL LIGAND WITH A MODEL CHANNEL
新型配体与模型通道的相互作用
- 批准号:
2910270 - 财政年份:1997
- 资助金额:
$ 10.36万 - 项目类别:
INTERACTIONS OF A NOVEL LIGAND WITH A MODEL CHANNEL
新型配体与模型通道的相互作用
- 批准号:
2701779 - 财政年份:1997
- 资助金额:
$ 10.36万 - 项目类别:
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