Urea moiety as amide bond mimetic in peptide-like inhibitors of VEGF-A/NRP-1 complex.

NRP-1 is an important co-receptor of vascular endothelial growth factor receptor-2 (VEGFR-2). Many reports suggested that NRP-1 might also serve as a separate receptor for VEGF-A causing stimulation of tumour growth and metastasis. Therefore, compounds interfering with VEGF-A/NRP-1 complex triggered interest in the design of new molecules, including peptides, as anti-angiogenic and anti-tumour drugs. Here, we report the synthesis, affinity and stability evaluation of the urea-peptide hybrids, based on general Lys(hArg)-AA-AA-Arg sequence, where hArg residue was substituted by Arg urea unit. Such substitution does not substantially affected affinity of compounds for NRP-1 but significantly increased their proteolytic stability in plasma.KEYWORDSAmide bond mimetic, Neuropilin-1, Peptidomimetics, Protein–ligand interaction, VEGF-A(165)Copyright © 2019 Elsevier Ltd. All rights reserved.