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-beta-alanyl-L-dopa (5-S-GA-L-D: 1) were synthesized via orthoquinones using tyrosinase. Several synthesized compounds inhibited the v-Src autophosphorylation tyrosine kinase reaction with an IC50 value comparable to that of herbimycin. The inhibition of c-Src substrate phosphorylation was much less active than v-Src autophosphorylation inhibition. The analogues showed no effects on substrate phosphorylation by epidermal growth factor receptor (EGFR), and this selectivity is the most characteristic feature of the analogues (1-12).
Zheng
Z B
ZB
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Nagai
S
S
Iwanami
N
N
Kobayashi
A
A
Hijikata
M
M
Natori
S
S
Sankawa
U
U
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D007980:Levodopa / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010766:Phosphorylation; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
C117123:5-S-glutathionyl-beta-alanyl-L-DOPA; D004791:Enzyme Inhibitors; D007980:Levodopa; D019061:src-Family Kinases; D005978:Glutathione