The aim of this research is to investigate the role of fertilinbeta and cyritestin in mammalian sperm-egg adhesion and fusion. Fertilinbeta and cyritestin are members of the ADAM family of proteins containing disintegrin domains. Monovalent peptide mimics of the fertilinbeta and cyritestin disintegrin domains are modest inhibitors of sperm-egg fusion. It is hypothesized that the modest inhibition of sperm-egg fusion by the mimics is a result of a monovalent binding interaction of low affinity. To address this interpretation, polyvalent inhibitors which mimic the cell surface display of fertilinbeta and cyritestin will be synthesized. These peptides will be constructed by synthesizing soluble peptide polymers using ring-opening metathesis polymerization. These peptide polymers will contain the sequences of fertilinbeta and cyritestin. This approach will address the avidity question by controlling not only the spatial arrangement of ligands but also the number of ligands presented. These peptide polymers will be tested using mice in an in vitro fertilization assay. We will then use immunofluorescence microscopy to investigate if these polyvalent peptides induce integrin aggregation. These polyvalent peptides will also be used to investigate the processes involved in egg activation. Fertilinbeta is present in every mammalian species screened thus far, including humans. Therefore, the information obtained from this work will have applications in developing new human contraceptive methods and in addressing problems of infertility.
