Research Support Core: Synthesis Core

研究支持核心：综合核心

• 批准号: 7936636
• 负责人: LARRY W ROBERTSON
• 金额: $ 20.55万
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7936636
• 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; 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.

综合核心通过提供多氯联苯接触混合物以及单个多氯联苯同系物和多氯联苯代谢物，直接支持衣阿华大学SBRP研究计划的研究功能。具体目标1是多氯联苯混合物的维护和分析标准的制备/维护。综合核心将作为多氯联苯技术混合物的储存库（例如，Aroclors 1242和1254）和合成PCB混合物，接近芝加哥空气中发现的平均PCB分布。此外，综合核心将保持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是合成多氯联苯同系物，用于研究项目1、2和5的体外和体内研究。这些多氯联苯同系物也将提供给分析核心，用于编制分析和质量控制/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。羟基化PCB代谢物将由项目#1、#2、#3和#5用于体外和体内研究。羟基化和甲氧基化多氯联苯衍生物也将作为分析标准品提供给分析中心，用于鉴别和定量（未知）代谢物。具体目标4包括合成用于isbrp的各种化合物，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。这一努力间接支持了项目#1、#2、#4、#5和#6。所有的化合物都将被合成，如果有必要的话，大量（克）的合成，直接的合成方法是在爱荷华大学建立良好的。利用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每个感兴趣的化合物的个人研究项目。