The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis

Yi Yong Baek, Dong Keon Lee, Ju Hoon So, Cheol Hee Kim, Dooil Jeoung, Hansoo Lee, Jongseon Choe, Moo Ho Won, Kwon Soo Ha, Young Guen Kwon, Young Myeong Kim

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)532-537
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume463
Issue number4
DOIs
Publication statusPublished - 2015 Jul 13

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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