Inhibition effects of 5-S-glutathionyl-N-beta-alanyl-L-dopa analogues against Src protein tyrosine kinase

Twelve analogues of the antibacterial phenolic peptide 5-S-glutathionyl-N-b eta-alanyl-L-dopa (5-S-GA-L-D, 1) were synthesized via orthoquinone using t yrosinase. Several synthesized compounds inhibited the v-Src autophosphoryl ation tyrosine kinase reaction with an IC50 value comparable to that of her bimycin A. The inhibition of c-Src substrate phosphorylation was much less active than v-Src autophosphorylation inhibition. 5-S-GA-L-D (1) and its an alogous competed with peptide substrate and non-competed with ATP. The anal ogues showed no effects on substrate phosphorylation by epidermal growth fa ctor receptor (EGFR), and this selectivity is the most characteristic featu re of the 5-S-GA-L-D and its analogues (1-12).