Chemical Synthesis and X-ray Structure of a Heterochiral {D-protein Antagonist Plus Vascular Endothelial Growth Factor} Protein Complex by Racemic Crystallography

K. Mandala, et al., 109(37), 14779-14784, Proc Natl Acad Sci USA, 2012

Mirror image phage display was applied as an approach to develop high affinity D-protein antagonists for a biologically active protein target. A D-protein ligand would be an optimal therapeutic - i.e. it can be manufactured, will be resistant to proteolytic degradation and will likely be non-immunogenic. Here, a specific D-protein ligand for VEGF-A was generated that blocks binding to the VEGFR1 receptor. X-ray structure of the antagonist-protein complex was determined. The Octet system was used to show specificity of protein ligand/VEGF-A interactions.

Read More