Development of withaferin A analogs as probes of angiogenesis
Copyright policy )Development of withaferin A analogs as probes of angiogenesis
The natural product withaferin A (WFA) is a potent angiogenesis inhibitor and it targets the ubiquitin-proteasome pathway in vascular endothelial cells. We generated a biotinylated affinity analog WFA-LC(2)B for use as a probe to study angiogenesis. WFA-LC(2)B inhibits angiogenic sprouting in vitro and it causes levels of ubiquitinated proteins to increase in tumor necrosis factor-alpha-treated human umbilical vein endothelial cells, confirming the retention of WFA's biological activity. We show that WFA-LC(2)B forms protein adducts in endothelial cells which are competed by free WFA in vivo. This WFA-LC(2)B analog will be useful to isolate the biological target of WFA.
- University of Kentucky United States
Ergosterol, Molecular Probes, Humans, Angiogenesis Inhibitors, Electrophoresis, Polyacrylamide Gel, Endothelium, Vascular, Withanolides, Cells, Cultured
Ergosterol, Molecular Probes, Humans, Angiogenesis Inhibitors, Electrophoresis, Polyacrylamide Gel, Endothelium, Vascular, Withanolides, Cells, Cultured
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