Protein-protein interactions that occur during fertilization will be investigated. Sperm-egg adhesion and fusion is a multi-step process. Two sperm proteins, fertilin-beta and cyritestin, members of the ADAM family of proteins (A Disintegrin and Metalloprotease), are involved in sperm-egg binding. Biochemical and genetic experiments suggest there are multiple ADAM receptors on the egg. .Chemical probes containing the fertilin-beta or cyritestin binding motifs presented in either monovalent or multivalent format have been developed. These multivalent fertilin-beta mimics are the most potent fertilin-beta-derived inhibitors of fertilization to date. Moreover, these polymers cause parthenogenic egg activation resulting in resumption of meiosis.
The aim of this proposal is to investigate the mechanism of action of these polymers, as well as cyritestin-derived polymers. The investigation will determine whether inhibition is due to direct competition with sperm binding or if it is due to activation of the egg block to polyspermy that results in blocking of sperm fusion. The structural requirements for inhibition versus activation will be identified as well as the egg receptors responsible. The determination of the mechanism(s) of action of the polymers will provide new leads for investigating egg-sperm adhesion, fusion, and activation of development. Understanding the mechanism of action of these compounds will provide insight into possible methods of controlling or aiding fertility.
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