Discovery, development, and testing of substrates and inhibitors of pp60(c-src)

Currently, there are no specific protein tyrosine kinase inhibitors available. This review summarizes our efforts to develop an active-site-directed inhibitor of pp60(c-src). Initial efforts are directed at determining substrate specificity with synthetic peptides and at developing a biological system to test the potential of pp60(c-src) inhibitors to effectively inhibit the growth of pp60(c-src) activated cell lines. To meet these goals, we have developed new methods for purifying recombinant pp60(c-src), assaying tyrosine kinase activity, synthesizing cyclic peptides, and generating random peptide libraries. In addition, we discuss the generation of potential artifacts while using polyhydroxy aromatic compounds as tyrosine kinase inhibitors.