Anandamide Carrier Proteins as Drug Targets

Anandamide 载体蛋白作为药物靶点

• 批准号: 8869089
• 负责人: Jason Jianxin Guo
• 金额: $ 38.63万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8869089
• 关键词: 2-arachidonylglycerol; AM1172; AM404; Affect; Affinity; Analgesics; Attenuated; Binding; Biochemical; Biological Assay; Blood - brain barrier anatomy; Brain; Carrier Proteins; Cellular Assay; Characteristics; Chemicals; Cloning; Data; Development; Disease; Docosahexaenoic Acids; Drug Addiction; Drug Targeting; Eating; Endocannabinoids; Escherichia coli; FABP5 gene; Future; Goals; Human; Hydrogen Bonding; Inclusion Bodies; Joints; Lead; Letters; Ligands; Lipids; Maps; Mass Spectrum Analysis; Methods; Modality; Modeling; Molecular Conformation; Molecular Probes; NMR Spectroscopy; Nuclear; Nuclear Magnetic Resonance; Pain; Pharmaceutical Preparations; Pharmacotherapy; Phase; Process; Property; Protein Family; Proteins; Quantitative Structure-Activity Relationship; Recombinants; Research; Rewards; Role; Signal Transduction; Site; Structure; Structure-Activity Relationship; Substance abuse problem; System; Testing; Variant; Work; Workplace; abstracting; analog; anandamide; biophysical techniques; design; drug candidate; fatty acid-binding proteins; human FABP5 protein; in vivo; inhibitor/antagonist; novel; novel therapeutics; pharmacophore; pi bond; research study; transport inhibitor; uptake

OTHER PROJECT INFORMATION - SECTION 7 - PROJECT SUMMARY/ABSTRACT The proposed research will explore the significance of intracellular carrier proteins in the transport of endocannabinoids and will develop novel ligands that can modulate brain endocannabinoid levels. Endocannabinoids, including anandamide and 2-arachidonoyl glycerol, are neurolipids involved in cell signaling. They affect pain sensing, food intake, and reward mechanisms. Specific transporter and/or carrier protein(s) have been implicated in the transport of endocannabinoids to their intracellular inactivation sites. In this proposal, we shall use nuclear magnetic resonance (NMR) spectroscopy to explore the structural and binding characteristics of two lipid carrier proteins, human brain fatty acid binding protein (FABP7) and epidermal FABP (FABP5), to a range of selected ligands including the endocannabinoids and several widely used endocannabinoid transport inhibitors. The information will be used to derive structure activity relationships (SAR) of these two target proteins. This SAR by NMR approach will guide the development of potent FABP7 ligands as well as FABP7/5 dual inhibitors as putative drug candidates which act through the elevation of endocannabinoid levels. The conclusion of the proposed research will lead to a greater understanding of the endocannabinoid system and represent first step towards a potential new pharmacotherapy utilizing the inhibition of FABPs as a new therapeutic modality for treating pain, substance abuse/drug addiction and other disorders.

其他项目信息 - 第7节 - 项目摘要/摘要 拟议的研究将探讨细胞内载体蛋白在运输中的重要性 内源性大麻素，并将开发可调节脑内源性大麻素水平的新型配体。 内源性大麻素，包括anandamide和2-芳基酮甘油，是参与细胞的神经脂质 信号。它们会影响疼痛感，食物摄入和奖励机制。特定运输蛋白和/或 载体蛋白（S）与内源性大麻素的运输有关 灭活地点。在此提案中，我们将使用核磁共振（NMR）光谱进行 探索两个脂质载体蛋白的结构和结合特性，即人类脑脂肪酸 结合蛋白（FABP7）和表皮FABP（FABP5）与一系列选定的配体（包括） 内源性大麻素和几种广泛使用的内源性大麻素转运抑制剂。信息将 用于得出这两个靶蛋白的结构活动关系（SAR）。这个sar by NMR方法将指导有效的FABP7配体以及Fabp7/5 Dual的开发 抑制剂作为推定的候选药物，通过内源性大麻素水平的升高作用。这 拟议的研究的结论将导致对内源性大麻素的更多了解 系统并代表了使用抑制的潜在新药物治疗的第一步 Fabps是一种治疗疼痛，药物滥用/吸毒和其他治疗的新治疗方式 疾病。