The overall goals of this project are to develop immunoassays for the detection of bryostatin 1 and its analogues in a variety of biological matrices. The bryostatins have exhibited strong antineoplastic activity in preclinical studies and are scheduled to enter Phase I clinical trials later this year. Sensitive analytical methods are needed for establishing the proper dosing regimens in these studies and for maximizing yields during the large scale isolation of these scarce natural products. In addition, the availability of bryostatin immunoassays would facilitate basic research efforts to determine the biosynthesis and actual source of these interesting compounds. We plan to synthesize well characterized bryostatin immunogens which should elicit antibody responses in rabbits and mice. The goal of Phase I research will be to demonstrate the feasibility of producing bryostatin immunoassays utilizing polyclonal rabbit antibodies. Phase II research will focus on refining these assays, production of additional monoclonal antibody-based immunoassays of varying specificities for particular applications, and developing procedures for determining bryostatin concentrations in various biological matricies.
