A FRET-based high throughput screening assay to identify inhibitors of anthrax protective antigen binding to capillary morphogenesis gene 2 protein.
A FRET-based high throughput screening assay to identify inhibitors of anthrax protective antigen binding to capillary morphogenesis gene 2 protein.
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DOI：
10.1371/journal.pone.0039911
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Christensen KA
中科院分区：
文献类型：
--
作者：
Rogers MS;Cryan LM;Habeshian KA;Bazinet L;Caldwell TP;Ackroyd PC;Christensen KA
Anti-angiogenic therapies are effective for the treatment of cancer, a variety of ocular diseases, and have potential benefits in cardiovascular disease, arthritis, and psoriasis. We have previously shown that anthrax protective antigen (PA), a non-pathogenic component of anthrax toxin, is an inhibitor of angiogenesis, apparently as a result of interaction with the cell surface receptors capillary morphogenesis gene 2 (CMG2) protein and tumor endothelial marker 8 (TEM8). Hence, molecules that bind the anthrax toxin receptors may be effective to slow or halt pathological vascular growth. Here we describe development and testing of an effective homogeneous steady-state fluorescence resonance energy transfer (FRET) high throughput screening assay designed to identify molecules that inhibit binding of PA to CMG2. Molecules identified in the screen can serve as potential lead compounds for the development of anti-angiogenic and anti-anthrax therapies. The assay to screen for inhibitors of this protein–protein interaction is sensitive and robust, with observed Z' values as high as 0.92. Preliminary screens conducted with a library of known bioactive compounds identified tannic acid and cisplatin as inhibitors of the PA-CMG2 interaction. We have confirmed that tannic acid both binds CMG2 and has anti-endothelial properties. In contrast, cisplatin appears to inhibit PA-CMG2 interaction by binding both PA and CMG2, and observed cisplatin anti-angiogenic effects are not mediated by interaction with CMG2. This work represents the first reported high throughput screening assay targeting CMG2 to identify possible inhibitors of both angiogenesis and anthrax intoxication.
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影响因子：
9.8
作者：
Adamis, A P;Aiello, L P;D'Amato, R A
通讯作者：
D'Amato, R A
影响因子：
5.7
作者：
Alvarez, Zodkiel;Abel-Sontos, Ernesto
通讯作者：
Abel-Sontos, Ernesto
影响因子：
5.7
作者：
Bijman, Marcel N. A.;van Nieuw Amerongen, Geerten P.;Boven, Epie
通讯作者：
Boven, Epie
DOI：
10.1083/jcb.200211018
发表时间：
2003-02-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Abrami L;Liu S;Cosson P;Leppla SH;van der Goot FG
通讯作者：
van der Goot FG
影响因子：
6.4
作者：
Cui, XZ;Li, Y;Eichacker, PQ
通讯作者：
Eichacker, PQ