Carbohydrate-based peptidomimetics targeting neuropilin-1: Synthesis, molecular docking study and in vitro biological activities

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• 作者：Mylè ; ne Richard^a ; ^b ; Alicia Chateau^c ; ^d ; Christian Jelsch^e ; ^f ; Claude Didierjean^e ; ^f ; Xavier Manival^g ; Christophe Charron^g ; Bernard Maigret^h ; Muriel Barberi-Heyob^c ; ^d ; Yves Chapleur^a ; ^b ; Cé ; dric Boura^c ; ^d ; Nadia Pellegrini-Moï ; se^a ; ^b ; ^{nadia.pellegrini@univ-lorraine.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MRI ; magnetic resonance imaging ; AKT ; serine/threonine protein kinase ; ERK1/2 ; extracellular signal-regulated protein kinases 1 and 2
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 November 2016
• 年：2016
• 卷：24
• 期：21
• 页码：5315-5325
• 全文大小：1695 K

文摘

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-A₁₆₅ binding to NRP-1 (IC₅₀ = 39 μM) 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.