Modulation of angiogenesis by a tetrameric tripeptide that antagonizes vascular endothelial growth factor receptor 1.

TitleModulation of angiogenesis by a tetrameric tripeptide that antagonizes vascular endothelial growth factor receptor 1.
Publication TypeJournal Article
Year of Publication2008
JournalThe Journal of biological chemistry
Volume283
Issue49
Pagination34250-9
Date Published2008 Dec 5
ISSN0021-9258
AbstractVascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1) is involved in complex biological processes often associated to severe pathological conditions like cancer, inflammation, and metastasis formation. Consequently, the search for antagonists of Flt-1 has recently gained a growing interest. Here we report the identification of a tetrameric tripeptide from a combinatorial peptide library built using non-natural amino acids, which binds Flt-1 and inhibits in vitro its interaction with placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) A and B (IC(50) approximately 10 microm). The peptide is stable in serum for 7 days and prevents both Flt-1 phosphorylation and the capillary-like tube formation of human primary endothelial cells stimulated by PlGF or VEGF-A. Conversely, the identified peptide does not interfere in VEGF-induced VEGFR-2 activation. In vivo, this peptide inhibits VEGF-A- and PlGF-induced neoangiogenesis in the chicken embryo chorioallantoic membrane assay. In contrast, in the cornea, where avascularity is maintained by high levels of expression of the soluble form of Flt-1 receptor (sFlt-1) that prevents the VEGF-A activity, the peptide is able to stimulate corneal mouse neovascularization in physiological condition, as reported previously for others neutralizing anti-Flt-1 molecules. This tetrameric tripeptide represents a new, promising compound for therapeutic approaches in pathologies where Flt-1 activation plays a crucial role.
URLhttp://www.jbc.org/cgi/pmidlookup?view=long&pmid=18922791
DOI10.1074/jbc.M806607200
PubMed Linkhttp://www.ncbi.nlm.nih.gov/pubmed/18922791?dopt=Abstract
Short TitleJ Biol Chem