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

Alexandre Novoa (1) , Nadia Pellegrini-Moïse (1) , Denise Bechet (2, 3) , Muriel Barberi-Heyob (2, 3) , Yves Chapleur (1)

1 SRSMC - Structure et Réactivité des Systèmes Moléculaires Complexes
2 CRAN - Centre de Recherche en Automatique de Nancy
3 CAV - Centre Alexis Vautrin

Neuropilin-1 (NRP-1) is a co-receptor of VEGFR165 and molecules interfering with VEGF165 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 μM, all compounds exhibited a weak affinity for NRP-1, the most efficient being the bis-guanidinylated compound 32 (IC50 = 92 μM) which could be considered as a new NRP-1 non-peptidic ligand. © 2010 Elsevier Science. All rights reserved

Mots clés: Neuropilin-1; Peptidomimetics; Scaffold; Carbohydrates

Domaines: Ingénierie biomédicale

Alexandre Novoa, Nadia Pellegrini-Moïse, Denise Bechet, Muriel Barberi-Heyob, Yves Chapleur. Sugar-based peptidomimetics as potential inhibitors of the vascular endothelium growth factor binding to neuropilin-1. Bioorganic and Medicinal Chemistry, 2010, 18 (8), pp.3285-3298. ⟨10.1016/j.bmc.2010.03.012⟩. ⟨hal-00476266⟩