ScFvs as Allosteric Inhibitors of VEGFR-2: Novel Tools to Harness VEGF Signaling.

ABSTRACT: Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) is the main mediator of angiogenic signaling in endothelial cells and a primary responder to VEGF. VEGF dependent VEGFR-2 activation regulates endothelial cell migration and proliferation, as well as vessel permeability. VEGF is presented as an antiparallel homodimer, and its binding to VEGFR-2 brings two receptors in close proximity. Downstream signaling is triggered by receptor dimerization, kinase activation, and receptor internalization. Our aim was to further investigate allosteric inhibition using binders targeting extracellular subdomains 4⁻7 of VEGFR-2 as an alternative to existing anti-angiogenic therapies, which rely on neutralizing VEGF or blocking of the ligand-binding site on the receptor. We applied phage display technol

SUBMITTER: Ballmer-Hofer K 

PROVIDER: S-EPMC5983656 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature