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Anti‐proliferative Properties of novel D‐Peptide‐VEGF‐Antagonists: Plausible Role in Anti‐angiogenic and Anti‐tumor Formation
Author(s) -
Rajashekhar Gangaraju,
Renwick Abby,
Cook Todd,
Vemula Sasidhar,
Kapur Rueben,
Schürmann Gregor,
Wagner Peter,
Clauss Matthias
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.634.5
Subject(s) - angiogenesis , in vivo , cancer research , peptide , bevacizumab , in vitro , chemistry , receptor , vascular endothelial growth factor , pharmacology , vegf receptors , biology , medicine , biochemistry , chemotherapy , microbiology and biotechnology
Interfering with VEGF binding to its endothelial receptor, VEGFR‐2 inhibits angiogenesis in tumors. Existing anti‐angiogenic peptide candidates, which efficiently compete with VEGF in binding of the VEGFR‐2 have been shown to demonstrate immunogenic and thromboembolic complications in clinical trials. D‐peptides against VEGF rather than the natural L‐form have the potential to overcome these problems faced by existing antibody‐based therapeutics. In this study, we attempted to screen for such a candidate peptide which has both antiangiogenic and anti‐tumor properties. A number of peptides were initially screened for anti‐proliferative capacity, a key step in angiogenesis using HUVEC cells both by coulter counter measurements and further confirmed with thymidine incorporation assays. Two candidate peptides were found to be dose dependently decreased the HUVEC proliferation in the presence of 1nM VEGF. When compared to Bevacizumab at 166nM, 07‐81‐1 and 07‐82‐1 at 30nM demonstrated a significant 35% and 27% reduction in proliferation respectively. Furthermore, these two peptides demonstrated a significant (p<0.05) inhibition at 300nM in an in vitro capillary sprout angiogenesis assay. Pending the analysis of these two candidate peptides in vivo for anti‐tumor properties, we will discuss the outcome in light of the fact that these peptides could be used to improve antiangiogenic tumor therapy.