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 journalArticlepeer-review

10 Citations (Scopus)


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
Issue number4
Publication statusPublished - 2015 Jul 13

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) (NRF- 2011-0028790 and 2013M3A9B6046563 ).

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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