Isoxazoles to Explore the Glutamate Receptors

异恶唑探索谷氨酸受体

• 批准号: 6471158
• 负责人: Nicholas R. Natale
• 金额: $ 14.85万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6471158
• 关键词: AMPA receptors; aminoacid analog; anticonvulsants; chemical models; chemical structure function; chemical synthesis; conformation; drug screening /evaluation; excitatory aminoacid; fluorescent dye /probe; glutamate receptor; high performance liquid chromatography; isoxazoles; neurotransmitter agonist; neurotransmitter antagonist; protein isoforms; receptor binding; receptor expression; stereochemistry

DESCRIPTION: (provided by applicant) Glutamate receptors are important in the transmision of signals across the synapses between nerve cells. Isoxazoles such as Amino-Methyl-Isoxazole Propionic Acid (AMPA) have been found to be useful in the characterization of Glutamate receptor subtypes. We have obtained results in the first granting period which show promise for the efficient preparation of chiral isoxazole glutamate receptor ligands. In the current granting period we propose (1) to complete the synthesis of a defined set of C(5) functionalized AMPA analogues based on structure based design using the G1uR2 subtype binding domain, (2) prepare linked antagonists and agonists to probe the Gouaux Glutamate receptor Activation and Antagonism model and (3) prepare glutamate receptor ligands covalently linked to molecular probes to help elucidate the conformation dynamics of the intact membrane bound receptor during activation and modulation.

描述：（由申请人提供）谷氨酸受体在 神经细胞之间的突触传递信号。异恶唑 如氨基-甲基-异恶唑丙酸（AMPA）， 可用于谷氨酸受体亚型的表征。我们所获得 结果在第一个授予期间，显示出有效的承诺， 手性异恶唑谷氨酸受体配体的制备。在当前 我们建议（1）完成一套确定的 C（5）官能化的AMPA类似物，其基于基于结构的设计， G1 uR 2亚型结合结构域，（2）制备连接的拮抗剂和激动剂， 探索Gouaux谷氨酸受体激活和拮抗模型，以及（3） 制备与分子探针共价连接的谷氨酸受体配体， 有助于阐明完整膜结合受体的构象动力学 在激活和调制期间。