Selective inhibition of Src protein tyrosine kinase by analogues of 5-S-glutathionyl-beta-alanyl-L-dopa

Twelve analogues of the antibacterial phenolic peptide 5-S-glutathionyl-bet a-alanyl-L-dopa (5-S-GA-L-D: 1) were synthesized via orthoquinones using ty rosinase, Several synthesized compounds inhibited the v-Src autophosphoryla tion tyrosine kinase reaction with an IC50 value comparable to that of herb imycin. The inhibition of c-Src substrate phosphorylation was much less act ive than v-Src autophosphorylation inhibition. The analogues showed no effe cts on substrate phosphorylation by epidermal growth factor receptor (EGFR) , and this selectivity is the most characteristic feature of the analogues (1-12).