Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10749971 | Biochemical and Biophysical Research Communications | 2015 | 6 Pages |
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 0.06-0.08Â nM, which was about ten-fold lower than that of the control peptide KLYD (0.79Â 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.
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Authors
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,