CORE--ORGANIC SYNTHESIS FACILITY

核心——有机合成装置

• 批准号: 6605471
• 负责人: SHANTU G AMIN
• 金额: $ 24.29万
• 依托单位: INSTITUTE FOR CANCER PREVENTION
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6605471
• 关键词: biomarker; biomedical facility; carcinogens; chemical synthesis; high performance liquid chromatography; mass spectrometry; organic chemicals; radiation detector; radionuclides

The Organic Synthesis Facility has grown into an integrated, essential part of the AHFCC research program in chemical, environmental, and endogenous carcinogenesis. It is equally involved in the Cancer Center's research on the chemoprevention of cancer, the development of biomarkers of uptake and metabolic activation of carcinogens, and the identification of etiologically significant host factors. Research activities of the Facility encompass the development of syntheses of carcinogens, their detoxification products, reactive species of metabolic activation, and DNA adducts formed with such species. The activities include the identification and synthesis of biomarkers of uptake and activation of environmental carcinogens that required deuterated, tritiated, and 14C- labeled isotopes. Needed agents are furnished to the Cancer Center's investigators for research projects supported by the NCI, NIDCR, NIEH, the Health Department of the Commonwealth of Massachusetts, and agencies such as the American Cancer Society. Requests amounts range from picograms for reference compounds to multigrams for large-scale bioassays. The structural integrity and purity of all agents is ensured by state-of-the-science technology, including HPLC, GC-MS, GC-TEA, TLC, UV, IR, FTIR, MS, and NMR. Scientists in the Facility are highly experienced in developing efficient synthetic routes for non-radiolabel and radioisotope-labeled polycyclic aromatic hydrocarbons, tobacco- specific N-nitrosamines, and other environmental and nutritional carcinogens, their metabolites, and their DNA adducts. The Organic Synthesis Facility occupies 900 ft/2 in Unit 1 and, for the synthesis of isotope-labeled compounds 447 ft/2 of laboratory space at the lower level of NDI. The Facility's dedicated Carcinogen Synthesis Laboratory is equipped with several HPLCs, including one instrument with a beta-flow model IC radioactivity detector, and with a medium pressure liquid chromatograph. These instruments enable the analysis and purification of starting materials, intermediates, and end products. The laboratory hoods are equipped with glove boxes. There is also a walk-in hood, as required by regulatory statutes. The dedicated Selenium Laboratory, in which chemopreventive agents are prepared, has a special exhaust system in compliance with safety regulations for these chemicals. The dedicated Synthesis Laboratory for intermediates, nucleoside markers, and chemopreventive agents (other than selenium) is equipped with a photolysis set-up, HPLC with photo diode array detector, and two working hoods with a 24-h exhaust system. Radiolabeled syntheses are carried out in a dedicated laboratory that is accessed only upon approval by the Cancer Center's Safety Officer who also supervises adherence to safety regulations.

有机合成设施已发展成为 AHFCC 化学、环境和内源性致癌研究项目的重要组成部分。它同样参与癌症中心的癌症化学预防、致癌物摄取和代谢激活生物标志物的开发以及具有病因学意义的宿主因素的鉴定等研究。该设施的研究活动包括开发致癌物的合成、其解毒产物、代谢活化的活性物质以及与这些物质形成的DNA加合物。这些活动包括识别和合成需要氘化、氚化和 14C 标记同位素的环境致癌物的吸收和激活的生物标志物。向癌症中心的研究人员提供所需的药物，以开展由 NCI、NIDCR、NIEH、马萨诸塞州卫生部以及美国癌症协会等机构支持的研究项目。请求量范围从参考化合物的皮克到大规模生物测定的多克。所有试剂的结构完整性和纯度均由最先进的技术确保，包括 HPLC、GC-MS、GC-TEA、TLC、UV、IR、FTIR、MS 和 NMR。该工厂的科学家在开发非放射性标记和放射性同位素标记的多环芳烃、烟草特有的 N-亚硝胺以及其他环境和营养致癌物、其代谢物及其 DNA 加合物的有效合成路线方面拥有丰富的经验。有机合成设施在 1 号单元中占地 900 平方英尺，用于合成同位素标记化合物，在 NDI 较低层的实验室空间占地 447 平方英尺。该设施的专用致癌物合成实验室配备了多台 HPLC，其中包括一台配有 beta 流型 IC 放射性检测器的仪器和一台中压液相色谱仪。这些仪器能够分析和纯化起始材料、中间体和最终产品。实验室通风橱配有手套箱。根据监管法规的要求，还有一个步入式抽油烟机。 专门的硒实验室负责制备化学预防剂，拥有符合这些化学品安全规定的特殊排气系统。 中间体、核苷标记物和化学预防剂（硒除外）的专用合成实验室配备了光解装置、带光电二极管阵列检测器的 HPLC 以及两个带 24 小时排气系统的工作罩。放射性标记合成是在专用实验室中进行的，该实验室只有在癌症中心安全官员批准后才能进入，该安全官员还监督安全法规的遵守情况。