Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 16, Issue 10, Pages 2603-2607Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2006.02.039
Keywords
biotinylated analog; natural product; binding protein; ubiquitin; angiogenesis inhibitor
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Funding
- NEI NIH HHS [R01 EY016782-02, R01 EY016782-04, R01 EY016782-05, R01 EY016782-01A2, R01 EY016782-03, R01 EY016782] Funding Source: Medline
- NINDS NIH HHS [NS053593, R21 NS053593] Funding Source: Medline
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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-LC2B for use as a probe to study angiogenesis. WFA-LC2B 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-LC2B forms protein adducts in endothelial cells which are competed by free WFA in vivo. This WFA-LC2B analog will be useful to isolate the biological target of WFA. (C) 2006 Elsevier Ltd. All rights reserved.
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