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-项目概要/摘要 这项研究将探讨细胞内载体蛋白在细胞内药物转运中的意义。 内源性大麻素，并将开发新的配体，可以调节大脑内源性大麻素水平。 内源性大麻素，包括大麻素和2-花生四烯酰甘油，是参与细胞凋亡的神经脂质。 发信号。它们影响疼痛感测、食物摄入和奖励机制。特定转运蛋白和/或 载体蛋白参与内源性大麻素向其细胞内的转运 失活位点。在这个建议中，我们将使用核磁共振（NMR）光谱， 探讨人脑脂肪酸两种脂质载体蛋白的结构和结合特性 结合蛋白（FABP7）和表皮FABP（FABP5），与一系列选择的配体，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。这些信息将 用于推导这两种靶蛋白的结构活性关系（SAR）。该SAR由 NMR方法将指导开发有效的FABP7配体以及FABP7/5双 抑制剂作为推定的候选药物，其通过提高内源性大麻素水平起作用。的 拟议研究的结论将导致对内源性大麻素的更好理解 系统，并代表了第一步走向一个潜在的新的药物疗法，利用抑制 FABPs作为治疗疼痛、物质滥用/药物成瘾和其他疾病的新治疗方式 紊乱