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We have filed a patent together with EvotecQAI to screen drugs interfering with protein-protein-interactions in live cells. PCT/EP 01/15265

Assay is based on the immobilised fusion protein GST-Ras G12V and the Alexa dye-labelled Ras binding domain of Raf kinase. Besides the detection of altered interaction by compounds, this assay also proved to be suitable for the potential identification of inducers of Ras GTPase activity. The system is stable for 24 hours at 30°C, can be scaled down to volumes of 1 to 5 µl quantities and in collaboration with EVOTEC OAI AG a 60,000 compound library has been screened.

The collaboration with EVOTEC OAI AG was successfully continued and using the assay described above more than 70.000 compounds were screened for their ability to either inhibit the Ras/Raf interaction or to induce GTPase activity of G12VRas. This work resulted in a patent (see also below), which claims to be capable of detecting reversible protein-protein interactions between GTPase negative forms of GTP-binding proteins and their effector's proteins.

In addition the system is capable of detecting chemical compounds that inhibit the above interactions in the living cell. In addition, the rescue of blocked GTPase activity can be detected. The system is potentially applicable to any pair of high-affinity or medium-affinity binding partner proteins.

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Contacto

Alfred WITTINGHOFER, (Professor)
Tel.: +49-231-1332100
Fax: +49-231-1332199
Correo electrónico
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