Urea-Peptide Hybrids as VEGF-A₁₆₅/NRP-1 Complex Inhibitors with Improved Receptor Affinity and Biological Properties.

ABSTRACT: Neuropilin-1 (NRP-1), the major co-receptor of vascular endothelial growth factor receptor-2 (VEGFR-2), may also independently act with VEGF-A₁₆₅ to stimulate tumour growth and metastasis. Therefore, there is great interest in compounds that can block VEGF-A165/NRP-1 interaction. Peptidomimetic type inhibitors represent a promising strategy in the treatment of NRP-1-related disorders. Here, we present the synthesis, affinity, enzymatic stability, molecular modeling and in vitro binding evaluation of the branched urea-peptide hybrids, based on our previously reported Lys(hArg)-Dab-Oic-Arg active sequence, where the Lys(hArg) branching has been modified by introducing urea units to replace the peptide bond at various positions. One of the resulting hybrids increased

SUBMITTER: Puszko AK 

PROVIDER: S-EPMC7793531 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature