Fate of a bioactive fluorescent wortmannin derivative in cells

KR Barnes, J Blois, A Smith, H Yuan… - Bioconjugate …, 2008 - ACS Publications
KR Barnes, J Blois, A Smith, H Yuan, F Reynolds, R Weissleder, LC Cantley, L Josephson
Bioconjugate chemistry, 2008ACS Publications
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 …
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.
ACS Publications