CORE--CHEMICAL AND ANALYTICAL

化学和分析核心将为个人研究项目提供支持。核心由两个部分组成：合成实验室和质谱设备。合成实验室将负责在持续的基础上，提供由计划项目确定的特定化合物的需求。由Core合成的化合物将用作定量标准，用于体外形成DNA和蛋白质加合物，用于体内给药方案。来自合成实验室的稳定同位素标记的标准倍数的可用性将对同位素稀释方法的发展至关重要，用于质谱设备对代谢物、DNA和蛋白质加合物的超痕量分析。已经确定需要合成的特定类别的化合物有：项目1，三环核碱基、脱氧核苷和脱氧核苷酸；丙二醛和4-羟基非-2-烯醛的蛋白质加合物半胱氨酸给药方案的持续基础；项目3和8，s -苯基- 5-半胱氨酸和巯基酸；项目4，多环芳烃的真菌代谢物，项目5,13c标记的多环芳烃酚。合成实验室还将提供有关结构表征问题的咨询，以及光谱技术在定量和表征问题中的应用。核心专业知识可能对计划项目有用的其他领域是将结构-活性关系应用于直接分离和表征代谢或非酶衰变产物的工作。Core拥有500和500 MHz核磁共振光谱仪，具有多核和变温能力。核心人员是训练有素的操作人员，精通数据采集，处理和解释的各个方面，并将填补程序项目的核磁共振需求。其他物理表征技术可以通过核心是圆二色x射线晶体学，EPR和FTIR。当质谱分析需求超出了项目所属设备的能力，或者需要开发广泛的方法时，质谱分析中心将为项目提供支持。质谱分析设施通过各种质谱技术进行常规的表征和超痕量分析，并参与开发工作。质谱分析设施的主要目标将是开发在线样品清理和分析物预浓缩程序，并应用HPLC/MS/MS技术来表征DNA加合物、蛋白质加合物和多环芳烃代谢物。

The Chemistry and Analytical Core will provide support for the individual research projects. The Core consists of two components: the Synthesis Laboratory and the Mass Spectrometry Facility. The Synthesis Laboratory will be responsible for providing, on a continuing basis, specific compounds for which need has been established by the Program Projects. Compounds synthesized by the Core will be used as standards in quantitation, for in vitro formation of DNA and protein adducts for in vivo dosing protocols. The availability of standards multiply labeled with stable isotopes from the Synthesis Laboratory will crucial to the development of isotope dilution methods for ultra-trace analysis of metabolites and DNA and protein adducts by the Mass Spectrometry Facility. Specific classes of compounds for which synthetic needs have been established are: Project 1, tricyclic nucleobases, deoxynucleosides and deoxynucleotides; protein adducts of malondialdehyde and 4-hydroxynon-2-enal; cysteine contual basis for dosing protocols; Projects 3 and 8, S-phenyl-d5-cysteine and mercapturic acid; Project 4, fungal metabolites of PAH and Project 5, 13C-labeled PAH phenoles. Synthesis Laboratory will also be available for consultation on questions involving structural characterizations, and application of spectroscopic techniques to problems of quantitation and characterization. Other areas where Core expertise may be useful to Program Projects are in the application of structure-activity relationships to direct efforts in isolation and characterization of products of metabolism or non-enzymatic decay. The Core has access to 500 and 500 MHz NMR spectrometers with multinuclear and variable temperature capability. Core personnel are trained operators, proficient in all aspects of data acquisition, work-up and interpretation, and will fill the NMR needs of program projects. Additional techniques of physical characterization accessible through the Core are circular dichroism X-ray crystallography, EPR and FTIR. The Mass Spectrometry Facility will provide support for Program Projects when mass spectrometry requirements are beyond the capacity of equipment belonging to Program Projects or when extensive methods development is necessary. The Mass Spectrometry Facility performs characterization and ultra-trace analysis on a routine basis by a variety of mass spectrometric techniques, and is also involved in developmental work. Major objectives of the Mass Spectrometry Facility will be to develop on-line sample clean-up and analyte pre-concentration procedures and to apply HPLC/MS/MS techniques to characterization of DNA adducts, protein adducts and PAH metabolites.