Sugar-based peptidomimetics as potential inhibitors of the vascular endothelium growth factor binding to neuropilin-1

Neuropilin-1 (NRP-1) is a co-receptor of VEGFR(165) and molecules interfering with VEGF(165) binding to NRP-1 seem to be promising candidates as new angiogenesis modulators. Based on the minimal four amino acid sequence of peptidic ligands known to bind NRP-1, we describe here the design, synthesis and biological evaluation of series of original sugar-based peptidomimetics using a C-glycosyl compound, derived from D-gulonolactone, as a scaffold, which was functionalized with side chains of the amino-acids arginine, and tryptophane or threonine. At 100 mu M, all compounds exhibited a weak affinity for NRP-1, the most efficient being the bis-guanidinylated compound 32 (IC50 = 92 mu M) which could be considered as a new NRP-1 non-peptidic ligand. (C) 2010 Elsevier Ltd. All rights reserved.