Carbohydrate-based peptidomimetics targeting neuropilin-1: Synthesis, molecular docking study and in vitro biological activities.
Neuropilin-1 (NRP-1), a transmembrane glycoprotein acting as a co-receptor of VEGF-A, is expressed by cancer and angiogenic endothelial cells and is involved in the angiogenesis process. Taking advantage of functionalities and stereodiversities of sugar derivatives, the design and the synthesis of carbohydrate based peptidomimetics are here described. One of these compounds (56) demonstrated inhibition of VEGF-A165binding to NRP-1 (IC50=39μM) and specificity for NRP-1 over VEGF-R2. Biological evaluations were performed on human umbilical vein endothelial cells (HUVECs) through activation of downstream proteins (AKT and ERK phosphorylation), viability/proliferation assays and in vitro measurements of anti-angiogenic abilities.
SRSMC UMR 7565, Université de Lorraine, BP 70239, F-54506 Vandœuvre-lès-Nancy, France; SRSMC UMR 7565, CNRS, BP 70239, F-54506 Vandœuvre-lès-Nancy, France.
Mylène
M
Richard
CRAN UMR 7039, Université de Lorraine, BP 70239, F-54506 Vandœuvre-lès-Nancy, France; CRAN UMR 7039, CNRS, BP 70239, F-54506 Vandœuvre-lès-Nancy, France.
Alicia
A
Chateau
CRM2 UMR 7036, Université de Lorraine, BP 70239, F-54506 Vandœuvre-lès-Nancy, France; CRM2 UMR 7036, CNRS, BP 70239, F-54506 Vandœuvre-lès-Nancy, France.
Christian
C
Jelsch
CRM2 UMR 7036, Université de Lorraine, BP 70239, F-54506 Vandœuvre-lès-Nancy, France; CRM2 UMR 7036, CNRS, BP 70239, F-54506 Vandœuvre-lès-Nancy, France.
Claude
C
Didierjean
IMoPA UMR 7365, Université de Lorraine, CS 50184, F-54505 Vandoeuvre-lès-Nancy, France.
Xavier
X
Manival
IMoPA UMR 7365, Université de Lorraine, CS 50184, F-54505 Vandoeuvre-lès-Nancy, France.
Christophe
C
Charron
UMR 7503 LORIA, BP 70239, 54506 Vandoeuvre-lès-Nancy, France.
Bernard
B
Maigret
CRAN UMR 7039, Université de Lorraine, BP 70239, F-54506 Vandœuvre-lès-Nancy, France; CRAN UMR 7039, CNRS, BP 70239, F-54506 Vandœuvre-lès-Nancy, France.
Muriel
M
Barberi-Heyob
SRSMC UMR 7565, Université de Lorraine, BP 70239, F-54506 Vandœuvre-lès-Nancy, France; SRSMC UMR 7565, CNRS, BP 70239, F-54506 Vandœuvre-lès-Nancy, France.
Yves
Y
Chapleur
CRAN UMR 7039, Université de Lorraine, BP 70239, F-54506 Vandœuvre-lès-Nancy, France; CRAN UMR 7039, CNRS, BP 70239, F-54506 Vandœuvre-lès-Nancy, France.
Cédric
C
Boura
SRSMC UMR 7565, Université de Lorraine, BP 70239, F-54506 Vandœuvre-lès-Nancy, France; SRSMC UMR 7565, CNRS, BP 70239, F-54506 Vandœuvre-lès-Nancy, France. Electronic address: nadia.pellegrini@univ-lorraine.fr.
Nadia
N
Pellegrini-Moïse
D002241:Carbohydrates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors*; D057786:Peptidomimetics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D002241:Carbohydrates; D057786:Peptidomimetics; D039942:Neuropilin-1
Carbohydrate scaffolds; Molecular modeling; Neuropilin-1; Peptidomimetics; VEGF