PUBLICATION
The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis
- Authors
- Baek, Y.Y., Lee, D.K., So, J.H., Kim, C.H., Jeoung, D., Lee, H., Choe, J., Won, M.H., Ha, K.S., Kwon, Y.G., Kim, Y.M.
- ID
- ZDB-PUB-150609-13
- Date
- 2015
- Source
- Biochemical and Biophysical Research Communications 463(4): 532-7 (Journal)
- Registered Authors
- So, Juhoon
- Keywords
- Angiogenesis, ERK, Endothelial cells, Tetrapeptide, eNOS
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Human Umbilical Vein Endothelial Cells
- Humans
- Neovascularization, Physiologic/drug effects*
- Oligopeptides/pharmacology*
- Sequence Homology, Amino Acid
- Signal Transduction/drug effects
- Vascular Endothelial Growth Factor A/pharmacology*
- Zebrafish
- PubMed
- 26051280 Full text @ Biochem. Biophys. Res. Commun.
Citation
Baek, Y.Y., Lee, D.K., So, J.H., Kim, C.H., Jeoung, D., Lee, H., Choe, J., Won, M.H., Ha, K.S., Kwon, Y.G., Kim, Y.M. (2015) The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis. Biochemical and Biophysical Research Communications. 463(4):532-7.
Abstract
Kringle 5, derived from plasminogen, is highly capable of inhibiting angiogenesis. Here, we have designed and synthesized 10 tetrapeptides, based on the amino acid properties of the core tetrapeptide Lys-Leu-Tyr-Asp (KLYD) originating from anti-angiogenic kringle 5 of human plasminogen. Of these, Arg-Leu-Tyr-Glu (RLYE) effectively inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration and tube formation, with an IC50 of 0.06-0.08 nM, which was about ten-fold lower than that of the control peptide KLYD (0.79 nM), as well as suppressed developmental angiogenesis in a zebrafish model. Furthermore, this peptide effectively inhibited the cellular events that precede angiogenesis, such as ERK and eNOS phosphorylation and nitric oxide production, in endothelial cells stimulated with VEGF. Collectively, these data demonstrate that RLYE is a potent anti-angiogenic peptide that targets the VEGF signaling pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping