Total chemical synthesis of the D2 domain of human VEGF receptor 1.

The interaction of the vascular endothelial growth factor (VEGF) with its cellular receptors exerts a central role in the regulation of angiogenesis. Among these receptors, the VEGF receptor 1 may be implicated in pathological angiogenesis. Here, we report the first total chemical synthesis of the VEGF-binding domain of the VEGF receptor 1. Aggregation issues were overcome by the use of a low-substituted resin and the stepwise introduction of pseudoproline dipeptides and Dmb-glycines. The folding of the protein was achieved by air oxidation and its biological activity was verified on ELISA-based assays.