Galloyl Carbohydrates with Antiangiogenic Activity Mediated by Capillary Morphogenesis Gene 2 (CMG2) Protein Binding.
Galloyl Carbohydrates with Antiangiogenic Activity Mediated by Capillary Morphogenesis Gene 2 (CMG2) Protein Binding.
复制标题
没食子酰碳水化合物具有由毛细血管形态发生基因 2 (CMG2) 蛋白结合介导的抗血管生成活性。
DOI：
10.1021/acs.jmedchem.8b01988
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发表时间：
2019
影响因子：
7.3
通讯作者：
Rogers,
中科院分区：
文献类型：
--
作者：
G-Doyagüez,Elisa;Carrero,Paula;Madrona,Andrés;Rodriguez-Salamanca,Patricia;Martínez-Gualda,Belén;Camarasa,MaríaJosé;Jimeno,MaríaLuisa;Bennallack,PhilipR;Finnell,JordanG;Tsang,Tsz-Ming;Christensen,KennethA;San-Félix,Ana;Rogers,
We previously showed that a small molecule of natural origin, 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose (PGG), binds to capillary morphogenesis gene 2 (CMG2) with a submicromolar IC50and also has antiangiogenic activity in vitro and in vivo. In this work, we synthetized derivatives of PGG with different sugar cores and phenolic substituents and tested these as angiogenesis inhibitors. In a high-throughput Förster resonant energy transfer-based binding assay, we found that one of our synthetic analogues (1,2,3,4,6-penta-O-galloyl-β-d-mannopyranose (PGM)), with mannose as central core and galloyl substituents, exhibit higher (up to 10×) affinity for CMG2 than the natural glucose prototype PGG and proved to be a potent angiogenesis inhibitor. These findings demonstrate that biochemical CMG2 binding in vitro predicts inhibition of endothelial cell migration ex vivo and antiangiogenic activity in vivo. The molecules herein described, and in particular PGM, might be useful prototypes for the development of novel agents for angiogenesis-dependent diseases, including blinding eye disease and cancer.
