Transforming growth factors (TGFs) are protein growth factors produced by transformed cells in culture. TGF is functionally related to epidermal growth factor and induces anchorage-independent growth of normal cells, a property closely associated with tumorigenicity. The amino acid sequence of the first such TGF from transformed rat fibroblasts has recently been determined. The immediate goals are to synthesize chemically this TGF and some selected analogs by the improved solid phase peptide synthesis. The long-range goal is to contribute to our understanding the cause and regulation of tumor by its own growth factors. The biological studies of transforming growth factors and, hence, rapid progress on the understanding of the detailed functional roles have been hampered by their scarcity. The proposed chemical synthesis of TGFs will provide a readily available source for its biochemical evaluations. Preliminary studies of the synthetic TGF include characterization of the physiological functions of TGF in whole organisms, identification of TGF receptors by photo-affinity labeling and its expression in transformed and embryonic cells. The synthesis of TGF analogs will aid the understanding, on the molecular level, of the interaction of TGF and its specific cellular receptor. Moreover analogs that function as inhibitors will provide an agent for the in vivo regulation of transforming growth factor activity and in general might be expected to provide a very different approach to the interruption of tumor cell progression. (J)
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