Core--Organic Synthesis - Synthesis of Lipid Mediators

核心--有机合成-脂质介体的合成

• 批准号: 6882274
• 负责人: NICOS A PETASIS
• 金额: $ 17.06万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6882274
• 关键词: biomedical facility; chemical structure; chemical synthesis; inflammation; lipids; organic chemicals; periodontium disorder; stereochemistry

The Chemistry Core will provide essential chemistry support for this Research Program through the synthesis and analysis of the specific novel lipid mediators being studied. This Core will be responsible for the chemical synthesis of the required quantities (up to milligram-scale) of a panel of bioactive lipoxins, resolvins, docosatrienes, presqualene diphosphate derivatives and related lipid mediators that will be used to study their role in the resolution of inflammation associated with periodontal disease. The Chemistry Core will develop and optimize the required synthetic pathways for the preparation of the selected lipid mediators in a stereochemically pure form and will carry out their total synthesis, detailed purification and structural verification. The Chemistry Core will also collaborate closely with the other Sub-Projects on the identification, structural elucidation and study of the targeted lipid mediators and will help prepare isotopically labeled derivatives for receptor binding studies. Overall, the work performed in the Chemistry Core is essential for studying the key actions of the lipid mediators studied in this Program, for elucidating the their role in the signaling pathways involved in resolution, and for establishing their potential "pro-resolution" and anti-inflammatory roles.

化学核心将通过合成和分析正在研究的特定新型脂质介质为本研究计划提供必要的化学支持。该核心将负责化学合成所需数量（高达毫克级）的一组生物活性脂氧素、消退素、二十二碳三烯、前角鲨烯二磷酸衍生物和相关脂质介质，这些介质将用于研究它们在解决牙周疾病相关炎症中的作用。化学核心将开发和优化所需的合成途径，以立体化学纯形式制备选定的脂质介质，并将进行全合成，详细纯化和结构验证。 化学核心还将与其他子项目密切合作，对靶向脂质介质进行鉴定、结构解析和研究，并将帮助制备用于受体结合研究的同位素标记衍生物。总体而言，在化学核心中进行的工作对于研究本计划中研究的脂质介质的关键作用，阐明其在参与解决的信号通路中的作用，以及建立其潜在的“促解决”和抗炎作用至关重要。