Development of withaferin A analogs as probes of angiogenesis

Yasuno Yokota, Paola Bargagna-Mohan, Padma P. Ravindranath, Kyung B. Kim, Royce Mohan

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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-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-α-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.

Original languageEnglish
Pages (from-to)2603-2607
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number10
DOIs
StatePublished - May 15 2006

Bibliographical note

Funding Information:
This work was supported by Fight-for-Sight Foundation Grant-in-Aid, Kentucky Tobacco Research & Development Center, and NIH (NS053593) grants to R.M. and a Research to Prevent Blindness Challenge Grant.

Keywords

  • Angiogenesis inhibitor
  • Binding protein
  • Biotinylated analog
  • Natural product
  • Ubiquitin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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