Research Support Core: Synthesis Core

研究支持核心：综合核心

• 批准号: 8884341
• 负责人: LARRY W ROBERTSON
• 金额: $ 0.08万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-12 至 2015-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8884341
• 关键词: Acetylcysteine; Air; Antigens; Chicago; Collaborations; Diazomethane; Glutathione; In Vitro; Individual; Inorganic Sulfates; Maintenance; Polychlorinated Biphenyls; Preparation; Quality Control; Quinones; Research; Research Project Grants; Research Support; Source; Toxic effect; Universities; Unspecified or Sulfate Ion Sulfates; Work; aroclor 1242; experience; in vivo; interest; programs; repository

The Synthesis Core directly supports the research function of the University of lowa SBRP research program (isbrp) by providing PCB exposure mixtures as well as individual PCB congeners and PCB metabolites. Specific Aim 1 is the maintenance of PCB mixtures and the preparation/maintenance of analytical standards. The Synthesis Core will serve as a repository for technical PCB mixtures (e.g., Aroclors 1242 and 1254) and a synthetic PCB mixture that approximates the average PCB profile found in Chicago air. In addition, the Synthesis Core will maintain analytical standards that are developed in close collaboration with the Analytical Core from pure PCB/PCB metabolites. Specific Aim 2 is the synthesis of PCB congeners for use with the in vitro and in vivo studies of Research Projects #1, #2 and # 5. These PCB congeners will also be available to the Analytical Core for the preparation of analytical and quality control/assurance standards. Specific Aim 3 is the synthesis of methoxylated and hydroxylated PCB metabolites. Hydroxylated PCB metabolites will be used by Projects #1, #2, #3, and #5 for in vitro and in vivo studies. Both the hydroxylated and methoxylated PCB derivatives will also be provided to the Analytical Core as analytical standards for the identification and quantification of (unknown) metabolites. Specific Aim 4 encompasses the synthesis of miscellaneous compounds for the isbrp, including PCB quinones (Projects #1, #2 and #3), PCB glutathione/N-acetyl cysteine conjugates (Project #1), PCB immunogens (Project #1) and PCB sulfates (Project #3). The Synthesis Core will also provide diazomethane as derivatization agent as part of this Aim. This effort indirectly supports Projects #1, #2, #4, #5 and #6. All compounds will be synthesized, if necessary in large (gram) quantities, with straightforward synthetic approaches that are well established at the University of lowa. Drawing on their extensive experience with the synthesis of organohalogen compounds. Synthesis Core staff will be able to synthesize every compound of interest to the individual Research Projects.

综合核心通过提供 PCB 暴露混合物以及单独的 PCB 同系物和 PCB 代谢物，直接支持洛瓦大学 SBRP 研究计划 (isbrp) 的研究功能。具体目标 1 是 PCB 混合物的维护以及分析标准品的制备/维护。合成核心将作为技术 PCB 混合物（例如 Aroclors 1242 和 1254）以及接近芝加哥空气中平均 PCB 分布的合成 PCB 混合物的存储库。此外，综合核心将维护与分析中心密切合作开发的分析标准。 核心来自纯 PCB/PCB 代谢物。具体目标 2 是合成 PCB 同源物，用于研究项目 #1、#2 和 #5 的体外和体内研究。这些 PCB 同源物也将可供分析核心用于准备分析和质量控制/保证标准。具体目标 3 是甲氧基化和羟基化 PCB 代谢物的合成。项目 #1、#2、#3 和 #5 将使用羟基化 PCB 代谢物进行体外和体内研究。羟基化和甲氧基化 PCB 衍生物也将提供给分析核心，作为（未知）代谢物鉴定和定量的分析标准品。具体目标 4 包括 isbrp 的各种化合物的合成，包括 PCB 醌（项目 #1、#2 和 #3）、PCB 谷胱甘肽/N-乙酰半胱氨酸缀合物（项目 #1）、PCB 免疫原（项目 #1）和 PCB 硫酸盐（项目 #3）。作为该目标的一部分，合成核心还将提供重氮甲烷作为衍生剂。这项工作间接支持项目#1、#2、#4、#5 和#6。如有必要，所有化合物都将采用洛瓦大学成熟的简单合成方法进行合成，如果需要大量（克）。借鉴他们在有机卤素化合物合成方面的丰富经验。合成核心工作人员将能够合成各个研究项目感兴趣的每种化合物。