Efficient synthesis of human type alpha transforming growth factor: its physical and biological characterization.

Abstract
Human transforming growth factor type .alpha. (TGF-.alpha.) was synthesized by a stepwise solid-phase method with an overall yield of 26%. Synthetic TGF-.alpha., consisting of 50 amino acid residues deduced from a cDNA precursor sequence, was purified in a single HPLC step. The homogeneity and primary structure were confirmed by several criteria including Edman degradation and mass spectrometry. Synthetic TGF-.alpha. was as active as murine epidermal growth factor in binding to the epidermal growth factor receptor and in stimulation of anchorage-dependent and of anchorage-independent growth of normal indicator cells in culture. Synthetic TGF-.alpha. stimulated plasminogen activator production in A 431 and HeLa cells; the stimulation was similar to that induced by epidermal growth factor. Furthermore, synthetic human TGF-.alpha. showed similar immunoreactivity when compared with rat TGF-.alpha.. Thus, the 50-amino acid TGF-.alpha. is likely to be the bioactive principle produced and secreted by tumor cell lines.