We will synthesize analogs of the thyroid hormones and test their binding affinities to soluble receptor preparations from rat liver cell nuclei, and to pure prealbumin from human plasma. We will synthesize analogs designed to maximize selective hormonal effects, such as the initiation of the developmental effects in the fetus. We will attempt to identify the specific nature of binding interactons between the hormone analogs and complementary groups on the protein, prealbumin. We will carry out parallel studies of analogs binding to prealbumin and to receptor, in order to characterize the nature of the receptor binding site. We will use the insight acquired to attempt to design and prepare a thyroid hormone antagonist.