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-beta-alanyl-L-dopa (5-S-GA-L-D, 1) were synthesized via orthoquinone using tyrosinase. Several synthesized compounds inhibited the v-Src autophosphorylation tyrosine kinase reaction with an IC50 value comparable to that of herbimycin 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 analogous competed with peptide substrate and non-compared with ATP. The analogues showed no effects on substrate phosphorylation by epidermal growth factor receptor (EGFR), and this selectivity is the most characteristic feature of the 5-S-GA-L-D and its analogues (1-12).
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Z B
ZB
Zheng
S
S
Nagai
N
N
Iwanami
A
A
Kobayashi
S
S
Natori
U
U
Sankawa
D016475:3T3 Cells; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D016227:Benzoquinones; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D007980:Levodopa / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D013379:Substrate Specificity; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
C117123:5-S-glutathionyl-beta-alanyl-L-DOPA; D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; D007980:Levodopa; C020754:herbimycin; D019061:src-Family Kinases; D005978:Glutathione