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

Chem Pharm Bull (Tokyo). 1999 Jun;47(6):777-82. doi: 10.1248/cpb.47.777.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Benzoquinones
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Glutathione / analogs & derivatives*
  • Glutathione / pharmacology
  • Lactams, Macrocyclic
  • Levodopa / analogs & derivatives*
  • Levodopa / pharmacology
  • Mice
  • Phosphorylation
  • Quinones / pharmacology
  • Rifabutin / analogs & derivatives
  • Substrate Specificity
  • src-Family Kinases / antagonists & inhibitors*

Substances

  • 5-S-glutathionyl-beta-alanyl-L-DOPA
  • Antibiotics, Antineoplastic
  • Benzoquinones
  • Enzyme Inhibitors
  • Lactams, Macrocyclic
  • Quinones
  • Rifabutin
  • Levodopa
  • herbimycin
  • src-Family Kinases
  • Glutathione