The focus of this research is to investigate protein-protein interactions that occur during mammalian fertilization. The ligand interactions that occur upon binding of the sperm protein fertilin to the egg plasma membrane, presumably at a receptor, will be dissected. Specifically, peptido-mimetics of the glutamate- cysteine-aspartate disintegrin loop and the epidermal growth factor-like module of fertilin will be synthesized and tested for their ability to inhibit sperm-egg fusion. Mutant peptides will be tested to identify residues important for inhibition and good inhibitors will be developed into affinity labels. These labels will be used to identify the receptor(s) in the egg-plasma membrane. Also, the domains of fertilin will be expressed using recombinant DNA methodology and will be tested for their ability to inhibit sperm-egg fusion. The domains will be used as affinity ligands for the isolation of their receptors and information about the structure of the domains will be obtained with NMR spectroscopy. Site-directed mutagenesis experiments will identify residues important for binding, fusion and signaling. The educational plan will focus on undergraduate course development and also on the development of a Ph.D. training program at the interface of chemistry and biology. With this CAREER award, the Synthetic Organic Program supports the research and educational activities of Dr. Nicole S. Sampson of the Department of Chemistry at SUNY, Stony Brook. Professor Sampson will focus her research efforts on investigating the protein-protein interactions that occur during mammalian fertilization. The benefit of the work lies in the development of better, more specific contraceptives and in discovering the genetic reasons for infertility which could then be circumvented. The educational plan will focus on the development of an undergraduate course on trends in biological chemistry and the the construction of a teaching plan for a Ph.D. training program at the interface of chemistry and biology.
