PROBES OF THE IMIDAZOLINE/GUANIDINIUM RECEPTOR

咪唑啉/胍受体探针

• 批准号: 3498696
• 负责人: John L Neumeyer
• 金额: $ 5万
• 依托单位: SIGMA-ALDRICH RESEARCH BIOCHEMICAL
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3498696
• 关键词: SDS polyacrylamide gel electrophoresis; adduct; affinity chromatography; affinity labeling; alpha adrenergic agent; analog; antiadrenergic agents; autoradiography; chemical binding; chemical reaction; chemical synthesis; drug design /synthesis /production; drug receptors; guanidines; hormone regulation /control mechanism; imidazole; intermolecular interaction; iodination; ligands; membrane proteins; molecular site; photochemistry; protein purification; protein structure; radiotracer; receptor binding

DESCRIPTION: (Adapted from Applicant's Abstract) The objective of this proposal is the synthesis and utilization of functionalized molecular probes specific for the imidazoline/guanidinium receptive site (IGRS), a potential important receptor involved in metabolic and cardiovascular regulation. IGRS-selective molecules will be chemically modified to generate 1) a radioiodinated ligand for cell-localization of IGRS and 2) a radioiodinated photoaffinity adduct for identification and structural characterization of the receptor's hormone binding subunit. Novel derivatives will also be synthesized for construction of an affinity matrix for protein purification. Imidazoline and guanidinium compounds such as clonidine and guanabenz elicit a wide variety of responses in both the central nervous system and peripheral tissues. Although many of these cellular effects are mediated by alpha2-adrenergic receptors, both functional and radioligand binding studies indicate that this class of pharmacologically active compounds interact with a cellular protein (IGRS) distinct from the alpha2-adrenergic receptor. Indeed, IGRS does not recognize catecholamines or other known neurotransmitters but does recognize an endogenous clonidine displacing substance purified from brain suggesting the existence of a previously unidentified hormonal/neurotransmitter-receptor system. Detailed analysis of this system and IGRS is limited by the lack of high-specific activity probes specific for the receptor protein.

描述：（改编自申请人的摘要） 提案是功能化分子的合成和利用 针对咪唑啉/鸟嘌呤接受部位（IGRS）的探针，A 代谢和心血管涉及的潜在重要受体 规定。 IGRS选择性分子将化学修改为 生成1）用于IGRS细胞平局的放射性碘化配体和2）A 识别和结构的放射性固定型光接触加合物 受体激素结合亚基的表征。 小说 衍生物也将合成用于构建亲和力矩阵 用于蛋白质纯化。 咪唑啉和鸟嘌呤化合物，例如可乐定和鸟根 在中枢神经系统和 外围组织。 尽管这些细胞效应中有许多是介导的 通过α2-肾上腺素受体，功能性和放射性物质结合 研究表明，这类具有药理学活性化合物 与与α2-肾上腺素能不同的细胞蛋白（IGRS）相互作用 受体。 确实，IGRS不认识儿茶酚胺或其他已知的 神经递质但确实识别内源性可乐定位移 从大脑中纯化的物质表明存在 身份不明的激素/神经递质 - 纤维纤维纤维系统。 详细分析 该系统和IGRS的限制受到缺乏高特异性活动的限制 对受体蛋白的特异性探针。