Assessment of biological activity of synthetic fragments of transforming growth factor-alpha

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Abstract
Transforming growth factor-alpha (TGF-α) is a single chain polypeptide hormone of 50 amino acids that stimulates growth of some human cancer cells via an autocrine mechanism. The domain(s) of TGF-α that bind and activate its receptor have not been reported. Hydrophilicity plots of TGF-α indicate three discrete sequences that are theoretically exposed on the hormone's surface and thus potentially able to interact with the TGF-α receptor. Fragments of TGF-α encompassing these hydrophilic domains were prepared by using solid-phase peptide synthesis (SPPS) techniques and purified by use of high performance liquid chromotography (HPLC). Assessment of biological activity of the TGF-α fragments indicated that none of the fragments significantly inhibited binding of EOF to the receptor, stimulated DNA synthesis of cells, inhibited EGF-induced DNA synthesis of cells, stimualted growth of cells in soft agar, or induced phosphorylation of the receptor or p35 protein. These results indicate that the receptor binding domain of TGF-α is not totally encompassed by any of the separate fragments tested and probably is formed by multiple separate regions of TGF-α.