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 microM, all compounds exhibited a weak affinity for NRP-1, the most efficient being the bis-guanidinylated compound 32 (IC(50)=92 microM) which could be considered as a new NRP-1 non-peptidic ligand.
Novoa
Alexandre
A
Groupe SUCRES, UMR 7565, Nancy Université-CNRS, BP 70239, F-54506 Vandoeuvre-lès-Nancy, France.
Pellegrini-Moïse
Nadia
N
Bechet
Denise
D
Barberi-Heyob
Muriel
M
Chapleur
Yves
Y
D043924:Angiogenesis Modulating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D032701:Biomimetics; D002241:Carbohydrates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D039942:Neuropilin-1 / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D043924:Angiogenesis Modulating Agents; D002241:Carbohydrates; D008024:Ligands; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1