ARRA: Biosynthetic Key Steps of Angucycline Antitumor Drugs

This supplement request is to obtain support for a summer undergraduate researcn stuaent. i nis si~uuerit will pursue studies outlined under Specific Aims I and 3 of the parent proposal, to further characterize the biosynthetic pathway of the anti-cancer antibiotic gilvocarcin V. The student will be involved in both (i) organic synthetic studies towards key biosynthetic intermediates or model analogues, and (ii) enzyme studies to investigate the synthetic compounds as substrates of selected enzymes. Synthetic model studies were not proposed in the parent grant, but are a logical extension of the proposed studies, and likely the only way to shed light into a biosynthetic black box performed by an enzyme complex. The addition of a summer student will accelerate and broaden the syntheses and the enzyme studies. The summer student will work closely with a post-doctoral researcher and a graduate student involved in these particular aspects of the project. The involvement of a summer student will expand the project to include more synthetic analogues that can be used for assaying three enzymes, a rota-isomerase, a methyltransferase and a glycosyltransferase. The synthetic compounds may also be useful to generate semisynthetic analogues of the parent drug. Students are recruited from a pool of applicants who apply to the Department of Pharmaceutical Sciences Summer Research Program for Undergraduates. These students are usually sophomore and junior students at a variety of regional comprehensive and undergraduate institutions, and are selected to the program based on their interest in exploring a career in the pharmaceutical sciences or pharmacy. A student has been offered and accepted a position in the program, and is tentatively assigned to the applicant's laboratory, pending funding support. The objective of this summer research program is stimulate interest in a scientific career and to identify and recruit the very best students into the graduate program in pharmaceutical sciences, and thereby promote and facilitate research in the pharmaceutical sciences.