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.

有机合成设施已经发展成为AHFCC在化学、环境和内源性致癌研究项目中不可或缺的组成部分。它同样参与了癌症中心的癌症化学预防研究，致癌物质摄取和代谢激活的生物标志物的开发，以及病原学上重要的宿主因素的鉴定。该设施的研究活动包括发展致癌物质的合成、它们的解毒产物、代谢激活的反应性物种以及与这些物种形成的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摄取和激活的生物标志物。在NCI、NIDCR、NIEH、马萨诸塞州联邦卫生部和美国癌症协会等机构支持的研究项目中，癌症中心的研究人员可以获得所需的试剂。要求的数量从参考化合物的皮克图到大规模生物测定的多图不等。所有试剂的结构完整性和纯度由最先进的技术保证，包括HPLC、GC-MS、GC-TEA、TLC、UV、IR、FTIR、MS和NMR。该设施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、烟草特异性n-亚硝胺和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经验丰富。1号单元的有机合成设施占地900英尺/平方英尺，在NDI较低的楼层，用于合成同位素标记化合物的实验室空间为447英尺/平方英尺。该设施的专用致癌物合成实验室配备了几台高效液相色谱仪，包括一台带有β流模型IC放射性检测器的仪器，以及一台中压液相色谱仪。这些仪器能够对原料、中间体和最终产品进行分析和纯化。实验室通风柜配有手套箱。根据监管法规的要求，还有一个步入式引擎盖。专门的硒实验室，化学预防剂的准备，有一个特殊的排气系统，符合这些化学品的安全规定。专门合成中间体、核苷标记物和化学预防剂（硒除外）的实验室配备了光解装置、带光电二极管阵列检测器的高效液相色谱（HPLC）和两个带24小时排气系统的工作罩。放射性标签合成是在一个专门的实验室进行的，只有在癌症中心的安全官员批准后才能进入，他也监督安全法规的遵守情况。