Functional and structural characterization of small molecule interactions with ion channels

小分子与离子通道相互作用的功能和结构表征

• 批准号: 49947431
• 负责人: Dr. Stefan Becker, since 8/2008
• 金额: --
• 依托单位: Max-Planck-Institut für biophysikalische Chemie (Karl-Friedrich-Bonhoeffer-Institut) (aufgelöst)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/49947431?language=en
• 关键词: Functional; structural; characterization; small; molecule

Goal of this research project is to rationally design small molecules that interact with ion channels and investigate their mechanism of action in detail. For this purpose, a variety of biophysical methods including electrophysiology and solid-state nuclear magnetic resonance (ssNMR) spectroscopy shall be combined to study the action of synthetically designed channel ligands at a structural and functional level. Structural analysis will be based on multidimensional ssNMR experiments with potassium channel - small molecule complexes in a lipid bilayer environment. The spectroscopic results will be complemented with both biochemical binding experiments and electrophysiological recordings including mammalian voltage-gated potassium channels of therapeutic interest. Combination of these experiments with synthetic organic chemistry will enable the design of novel pharmacological compounds relevant for the treatment of a variety of human diseases and should lead to novel molecular tools for modulating electrical properties of neurons.

本研究的目的是合理设计与离子通道相互作用的小分子，并详细研究其作用机制。为此，应结合各种生物物理方法，包括电生理学和固态核磁共振（ssNMR）光谱，以研究合成设计的通道配体在结构和功能水平上的作用。结构分析将基于脂质双层环境中钾通道-小分子复合物的多维ssNMR实验。光谱结果将补充与生化结合实验和电生理记录，包括哺乳动物电压门控钾通道的治疗利益。将这些实验与合成有机化学相结合，将能够设计与治疗各种人类疾病相关的新型药理学化合物，并将导致用于调节神经元电特性的新型分子工具。