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ID: ALA1147689
Journal: Bioorg Med Chem Lett
Title: Development of withaferin A analogs as probes of angiogenesis.
Authors: Yokota Y, Bargagna-Mohan P, Ravindranath PP, Kim KB, Mohan R.
Abstract: 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.
CiteXplore: 16513346