CHEMICAL BIOLOGY OF NON-NATURAL ISOTHIOCYANATES AGAINST CANCER

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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。硫代葡萄糖苷是黑芥子酶的底物，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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.