Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction

…, A Garza-Garcia, N Winfield, K Ellard…

Index: Jarvis, Ashley; Allerston, Charles K.; Jia, Haiyan; Herzog, Birger; Garza-Garcia, Acely; Winfield, Natalie; Ellard, Katie; Aqil, Rehan; Lynch, Rosemary; Chapman, Chris; Hartzoulakis, Basil; Nally, James; Stewart, Mark; Cheng, Lili; Menon, Malini; Tickner, Michelle; Djordjevic, Snezana; Driscoll, Paul C.; Zachary, Ian; Selwood, David L. Journal of Medicinal Chemistry, 2010 , vol. 53, # 5 p. 2215 - 2226

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Citation Number: 71

Abstract

We report the molecular design and synthesis of EG00229, 2, the first small molecule ligand for the VEGF-A receptor neuropilin 1 (NRP1) and the structural characterization of NRP1− ligand complexes by NMR spectroscopy and X-ray crystallography. Mutagenesis studies localized VEGF-A binding in the NRP1 b1 domain and a peptide fragment of VEGF-A was shown to bind at the same site by NMR, providing the basis for small molecule design. ...