Development of withaferin A analogs as probes of angiogenesis

Yasuno Yokota, Yokota Y, Paola Bargagna-Mohan, Bargagna-Mohan P, Padma P Ravindranath, Ravindranath PP, Kim KB, Kyung B Kim, Royce Mohan, Mohan R
Bioorganic & medicinal chemistry letters · 2006 · vol. 16(10) , pp. 2603–7 · doi:10.1016/j.bmcl.2006.02.039 · PMID:16513346 · PMC3222585
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Researchers developed a biotinylated withaferin A analog to probe angiogenesis, demonstrating that it retains the parent compound's ability to inhibit endothelial sprouting and form protein adducts.

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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.

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MeSH descriptors

Angiogenesis Inhibitors Ergosterol Molecular Probes Angiogenesis Inhibitors Angiogenesis Inhibitors Cells, Cultured Electrophoresis, Polyacrylamide Gel Endothelium, Vascular Endothelium, Vascular Endothelium, Vascular Ergosterol Ergosterol Ergosterol Humans Withanolides

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europepmc
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pubmed
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