Fate of a bioactive fluorescent wortmannin derivative in cells

Bioconjug Chem. 2008 Jan;19(1):130-7. doi: 10.1021/bc7002204. Epub 2007 Nov 8.

Abstract

Here, we report on NBD-Wm, a fluorescent wortmannin (Wm) probe that maintains the bioactivity of Wm as an inhibitor of PI3 kinase and as an antiproliferative agent. The attachment of the NBD fluorochrome permits NBD-Wm in cells to be monitored by NBD fluorescence-based methods such as FACS or fluorescence microscopy or with an anti-NBD antibody. The fluorescence of NBD-Wm treated cells reached a peak at 1.5 h and then decreased because of the extrusion of a fluorescent compound into the culture media. Cells accumulated NBD-Wm to levels about 30-fold higher than those in the media. NBD-Wm modified five major proteins, with the modification of the catalytic subunit of PI3 kinase being a minor band. The bioactivity of NBD-Wm, coupled with a variety of techniques available for determining its disposition, suggest that NBD-Wm can be a useful tool in understanding the mechanism of action of viridins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Androstadienes / metabolism*
  • Androstadienes / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Fluorescent Dyes / metabolism*
  • Humans
  • Intracellular Space / metabolism
  • Oxadiazoles / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Time Factors
  • Wortmannin

Substances

  • Androstadienes
  • Fluorescent Dyes
  • Oxadiazoles
  • Phosphoinositide-3 Kinase Inhibitors
  • 4-nitrobenzofurazan
  • Wortmannin