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

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.

authors

Baek YY,Lee DK,So JH,Kim CH,Jeoung D,Lee H,Choe J,Won MH,Ha KS,Kwon YG,Kim YM

doi

10.1016/j.bbrc.2015.05.073

subject

Has Abstract

pub_date

2015-08-07 00:00:00

pages

532-7

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(15)30002-4

journal_volume

463

pub_type

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