CHEMICAL BIOLOGY OF NON-NATURAL ISOTHIOCYANATES AGAINST CANCER

非天然异硫氰酸盐抗癌的化学生物学

• 批准号: 8168030
• 负责人: Jared Ray Mays
• 金额: $ 4.92万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168030
• 关键词: Biology; Brassica; Broccoli - dietary; Cell Culture Techniques; Chemicals; Chemistry; Chemopreventive Agent; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Consumption; DNA Sequence Rearrangement; Enzymatic Biochemistry; Funding; Gastrointestinal tract structure; Glucosinolates; Grant; Hydrolysis; Incidence; Institution; Isothiocyanates; Malignant Neoplasms; Molecular Biology; Myrosinase; Organic Synthesis; Pharmaceutical Preparations; Physiological; Phytochemical; Process; Property; Research; Research Personnel; Resources; Source; Students; Sulforaphane; Training; United States National Institutes of Health; Vegetables; cruciferous vegetable; drug candidate; enzyme substrate; fruits and vegetables; interest; programs

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Consumption of fruits and vegetables has been associated with reduced incidence of cancer, especially in the gastrointestinal tract. The Brassica vegetables are rich sources of glucosinolate; evidence suggests that these phytochemicals are indirectly responsible for the observed cancer chemopreventive properties of cruciferous vegetables. Glucosinolates are substrates of the enzyme myrosinase, which catalyzes the hydrolysis of the glucosinolate thioglucosidic linkage to form an unstable intermediate that degrades to a variety of bioactive products. At physiological pH, this intermediate predominantly undergoes a Lossen rearrangement to form the respective isothiocyanates. Although glucosinolates themselves have no known bioactivity, many of their corresponding organic ITCs are well-documented chemopreventive agents. In particular, the isothiocyanate L-sulforaphane is the primary chemopreventive agent found in broccoli. Our research group is interested in exploiting the myrosinase/glucosinolate enzymatic processes as a means of achieving selective drug or drug candidate activation. This multi-disciplinary research program will bridge the boundaries between chemistry and biology and offer students the opportunity for training in several fields of research. Multiple student projects are available with differential and cross-emphases including multi-step organic synthesis, cell culture, molecular biology, enzymology, and computational modeling.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 食用水果和蔬菜与降低癌症发病率有关，特别是在胃肠道。十字花科蔬菜含有丰富的硫代葡萄糖苷；有证据表明，这些植物化学物质间接导致了十字花科蔬菜所观察到的癌症化学预防特性。硫代葡萄糖苷是酪氨酸酶的底物，该酶催化硫代葡萄糖苷键的水解形成一种不稳定的中间体，可降解为各种生物活性产物。在生理pH下，这个中间体主要进行Lossen重排，形成各自的异硫氰酸酯。尽管硫代葡萄糖苷本身没有已知的生物活性，但它们对应的许多有机ITC都是有充分证据的化学预防药物。特别是，异硫氰酸酯L-萝卜硫醚是在西兰花中发现的主要化学防腐剂。 我们的研究小组感兴趣的是利用黑芥子酶/硫代葡萄糖苷酶过程作为实现选择性药物或候选药物激活的一种手段。这一多学科的研究计划将在化学和生物之间架起一座桥梁，并为学生提供在几个研究领域进行培训的机会。多个学生专题有不同的和交叉的重点，包括多步骤有机合成、细胞培养、分子生物学、酶学和计算建模。