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Galloyl Carbohydrates with Antiangiogenic Activity Mediated by Capillary Morphogenesis Gene 2 (CMG2) Protein Binding. | LitMetric

AI Article Synopsis

  • Researchers studied a natural compound, PGG, which binds to the CMG2 protein and shows antiangiogenic effects, meaning it can inhibit blood vessel formation.
  • They created different derivatives of PGG and discovered one, PGM, that binds to CMG2 even more strongly (up to 10 times) and effectively inhibits angiogenesis.
  • The study suggests that these compounds, especially PGM, could lead to new treatments for diseases that involve abnormal blood vessel growth, like certain cancers and eye diseases.

Article Abstract

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 IC and 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859974PMC
http://dx.doi.org/10.1021/acs.jmedchem.8b01988DOI Listing

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