Fate of a bioactive fluorescent wortmannin derivative in cells

被引：16

作者：

Barnes, Katie R. ^{[1
,2
]}

Blois, Joseph ^{[1
,2
]}

Smith, Adam ^{[1
,2
]}

Yuan, Hushan ^{[1
,2
]}

Reynolds, Fred ^{[1
,2
]}

Weissleder, Ralph ^{[1
,2
]}

Cantley, Lewis C. ^{[3
]}

Josephson, Lee ^{[1
,2
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA

[2] Harvard Univ, Sch Med, Dept Syst Biol, Charlestown, MA 02129 USA

[3] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA

来源：

BIOCONJUGATE CHEMISTRY | 2008年 / 19卷 / 01期

关键词：

D O I：

10.1021/bc7002204

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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 N-BD-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.

引用

页码：130 / 137

页数：8

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