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.
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