Molecular Recognition of Potassium Channels

钾通道的分子识别

• 批准号: 6772779
• 负责人: DIRK HARTWIG TRAUNER
• 金额: $ 25.03万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6772779
• 关键词: Xenopus oocyte; cell line; chemical binding; chemical synthesis; drug discovery /isolation; fluorescence resonance energy transfer; ligands; membrane proteins; molecular probes; peptide library; pharmacokinetics; porphyrins; potassium channel; protein binding; structural biology; voltage gated channel

DESCRIPTION (provided by applicant): The goal of this research proposal is to combine organic synthesis with recent advances in structural biology to make significant contributions both to the fields of molecular recognition and neurobiology. We propose to develop fourfold symmetrical, synthetic ligands that recognize tetrameric ion channels, in particular potassium channels. The primary goal of the proposed research is to provide a large set of molecular probes that discriminate among different types of potassium channels or modulate their functional properties. These compounds could be useful tools in neurobiological studies. It is hoped that these compounds will eventually surpass antibodies and peptide toxins in the selective recognition of potassium channels. Ultimately, the proposed research might lead to novel therapeutic agents against various ailments such as autoimmune disorders, diabetes as well as mental or cardiac diseases. Specifically, the synthesis and biological evaluation of designed ligands for voltage-gated potassium channels such as KvAP, Shaker, and human Kv1.x channels is proposed. Pharmacologically relevant Kv1.x channels such as Kv1.3 or Kv1.5 will receive special attention. The ability of the synthetic ligands to bind to different functional states of a given channel will be evaluated.

描述（由申请人提供）：本研究计划的目标是将有机合成与结构生物学的最新进展相结合，为分子识别和神经生物学领域做出重大贡献。 我们建议开发四重对称的合成配体来识别四聚体离子通道，特别是钾通道。拟议研究的主要目标是提供大量分子探针，以区分不同类型的钾通道或调节其功能特性。这些化合物可能是神经生物学研究中有用的工具。希望这些化合物最终在钾通道的选择性识别方面超越抗体和肽毒素。最终，拟议的研究可能会产生针对各种疾病的新型治疗剂，例如自身免疫性疾病、糖尿病以及精神或心脏病。 具体来说，提出了电压门控钾通道（例如 KvAP、Shaker 和人 Kv1.x 通道）的设计配体的合成和生物学评估。药理学相关的 Kv1.x 通道（例如 Kv1.3 或 Kv1.5）将受到特别关注。将评估合成配体与给定通道的不同功能状态结合的能力。