Design, synthesis and in vitro biological evaluation of a small cyclic peptide as inhibitor of vascular endothelial growth factor binding to neuropilin-1

https://doi.org/10.1016/j.bmcl.2016.04.059Get rights and content

Abstract

Neuropilin-1 (NRP-1) is a co-receptor of VEGFR (vascular endothelial growth factor receptor), but it is also suggested that NRP-1 in tumour cells may serve as a separate receptor for VEGF165. Therefore molecules interfering with VEGF165 binding to NRP-1 seem to be promising candidates as new anti-angiogenic and anti-tumour drugs. Here, we report the design, synthesis, biological evaluation and molecular modelling of the small cyclic peptide, which shows a good inhibitory effect on VEGF165/NRP-1 binding (IC50 = 0.18 μM). The reported compound could be considered as one of the smallest cyclic peptides (MW = 510) interfering with VEGF165/NRP-1 binding presented up to now.

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Acknowledgments

This work was supported by National Science Centre (NCN) – Poland grant N204 350940 and co-financed by the EU from the European Regional Development Fund under the Operational Programme Innovative Economy, 2007–2013, and with the use of CePT infrastructure financed by the same EU program and a grant from the University of Warsaw – Poland for young researchers, no. 12000-501/86-DSM-107500. Molecular modelling was supported by Computational Grant G63-10 from the Interdisciplinary Centre for

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