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.
Goncalves
Victor
V
Université Paris Descartes, UFR biomédicale, Laboratoire de Pharmacochimie Moléculaire et Cellulaire, Paris, F-75006, France.
Gautier
Benoit
B
Huguenot
Florent
F
Leproux
Pascale
P
Garbay
Christiane
C
Vidal
Michel
M
Inguimbert
Nicolas
N
D006801:Humans; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D011392:Proline / Q000031:analogs & derivatives / Q000737:chemistry; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013844:Thiazoles / Q000737:chemistry; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000737:chemistry*
D010455:Peptides; D013844:Thiazoles; C505976:pseudoproline; D011392:Proline; D040281:Vascular Endothelial Growth Factor Receptor-1