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SYNTHESIS OF CONSTITUTIVELY ACTIVE SEROTONIN RECEPTORS

SYNTHESIS OF CONSTITUTIVELY ACTIVE SEROTONIN RECEPTORS
组成型活性血清素受体的合成
批准号:
2591718
负责人:
Pamela Michael England
金额:
$3.02万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
未结题
起止时间:
1997-11-01 至

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中文摘要
翻译
这项研究的主要目标是探索结构- 5-羟色胺1型(5 HT 1)受体内的功能关系 激动剂结合位点。为实现这一目标,将努力 通过以下方式明确识别神经递质结合位点: 组成型激活5-羟色胺结合位点的受体。 本研究的最终目的是将这些理论与实践有机地结合起来, 活性受体,以研究5 HT 1受体的长期作用 activation.该提案特别侧重于 将非天然氨基酸掺入5 HT 1A受体及其 在完整细胞中表达。 以下是研究 目标: L.设计和合成非天然氨基酸,包括 血清素本身在它们的侧链中。 2.将这些非天然氨基酸掺入到假定的 使用无义密码子抑制的5 HT 1A激动剂结合位点 非天然氨基酸掺入非洲爪蟾卵母细胞的方法。 3.功能性5 HT 1A受体的鉴定 电生理学分析功能耦合,共表达 鸟嘌呤结合蛋白(G蛋白)激活,内向整流 钾离子通道。
英文摘要
The primary goal of the proposed research is to probe structure- function relationships within the serotonin type 1 (5HT1) receptor agonist binding site. To achieve this goal, efforts will be made to unambiguously identify the neurotransmitter binding site by constitutively activating the receptor at the serotonin binding site. The ultimate goal of this research is to use these constitutively active receptors to study the long-term effects of 5HT1 receptor activation. This proposal is specifically focused on the incorporation of unnatural amino acids into 5HT1A receptors and their expression in intact cells. The following are the research objectives: l. Design and synthesis of unnatural amino acids that include serotonin itself in their side chains. 2. Incorporation of these unnatural amino acids into the putative 5HT1A agonist binding site using the nonsense codon suppression method for unnatural amino acid incorporation in Xenopus oocytes. 3. Identification of functional 5HT1A receptors through electrophysiological analysis of functionally coupled, coexpressed guanine binding protein (G-protein) activated, inwardly rectifying potassium (K+) channels.
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DOI: 10.1016/j.brainres.2012.10.050
发表时间: 2013-01-23
期刊: Brain research
影响因子: 2.9
作者: [Torterolo P, Sampogna S, Chase MH]
通讯作者: Chase MH
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