Design, synthesis and in vitro biological evaluation of a small cyclic peptide as inhibitor of vascular endothelial growth factor binding to neuropilin-1

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• 作者：Karolina Grabowska^a ; Anna K. Puszko^a ; Piotr F.J. Lipiński^b ; Anna K. Laskowska^b ; Beata Wileńska^a ; Ewa Witkowska^a ; Aleksandra Misicka^a ;
• 关键词：ABTS ; 2 ; 2&prime ; -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt ; BSA ; bovine serum albumin ; (bt)-VEGF165 ; biotinylated-VEGF165 ; 6-Cl· ; HOBt ; 6-chloro-1-hydroxybenzotriazole dehydrate ; DIPEA ; N ; N-diisopropylethylamine ; ELISA ; enzyme-linked immunosorbent assay ; HUVEC ; Human Umbilical Vein Endothelial Cells ; MDA-MB-231 ; human breast adenocarcinoma cells ; MTS ; 3-(4 ; 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt ; PBS ; phosphate buffered
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：26
• 期：12
• 页码：2843-2846
• 全文大小：781 K

文摘

Neuropilin-1 (NRP-1) is a co-receptor of VEGFR (vascular endothelial growth factor receptor), but it is also suggested that NRP-1 in tumour cells may serve as a separate receptor for VEGF₁₆₅. Therefore molecules interfering with VEGF₁₆₅ binding to NRP-1 seem to be promising candidates as new anti-angiogenic and anti-tumour drugs. Here, we report the design, synthesis, biological evaluation and molecular modelling of the small cyclic peptide, which shows a good inhibitory effect on VEGF₁₆₅/NRP-1 binding (IC₅₀ = 0.18 μM). The reported compound could be considered as one of the smallest cyclic peptides (MW = 510) interfering with VEGF₁₆₅/NRP-1 binding presented up to now.