Potent inhibition of angiogenesis by D,L-peptides derived from vascular endothelial growth factor receptor 2.

Abstract:

:Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells and plays a central role in angiogenesis and vasculogenesis. Therefore, VEGF and its receptors VEGFR-1 and VEGFR-2 are prime targets for anti-angiogenic intervention which is thought to be one of the most promising approaches in cancer therapy. Recently, we have discovered a VEGFR-2-derived peptide ((247)RTELNVGIDFNWEYP(261)) representing a potential binding site to VEGF. Using the spot synthesis technique, systematic D-amino acid substitutional analyses of this peptide were conducted and the resulting D,L-peptides inhibit VEGF binding to VEGFR-2 at half maximal concentration of 30 nM. The serum-stable D,L-peptides further inhibited autophosphorylation of the VEGFR-2 at nanomolar concentrations. Testing of the peptides in a spheroid-based angiogenesis assay demonstrated a potent anti-angiogenic effect in vitro. The rational design of potent and stable anti-angiogenic peptide inhibitors from their parent receptors provides a feasible route to develop novel leads for anti-angiogenic medicines.

journal_name

Thromb Haemost

authors

Piossek C,Thierauch KH,Schneider-Mergener J,Volkmer-Engert R,Bachmann MF,Korff T,Augustin HG,Germeroth L

doi

10.1160/TH03-02-0106

keywords:

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

501-10

issue

3

eissn

0340-6245

issn

2567-689X

pii

03090501

journal_volume

90

pub_type

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