Field
      Health Care, Method
Keywords
      Method, Protein-Protein-Interactions picture


Intention
 Protein-protein interactions are essential in many biological process including cell cycle and apoptosis. It is currently of great medical interest to inhibit specific protein-protein interactions in order to treat a variety of disease states.
Here, we describe a facile multiwell plate assay method using T7 phage display to screen for candidate inhibitors of protein-protein interactions. Because T7 phage display is an effective method for detecting protein-protein interactions, we aimed to utilize this technique to screen for small-molecule inhibitors that disrupt these types of interaction.
We used the well-characterized interaction between p53 and MDM2 and an inhibitor of this interaction, nutlin 3, as a model system to establish a new screening method. Phage particles displaying p53 interlaced with GST-MDM2 immobilized on 96-well plates, and the interaction was inhibited by nutlin3. Multiwell plate assay was then performed using a natural product library, which identified dehydroaltenusin as a candidate inhibitor of the p53-MDM2 interaction.
We want to help development of medical supplies with this technology. Therefore we wish the technology transfer to a partner's company, or an acceptance of the researcher from a company.


Inventor
    Prof. Fumio Sugawara. (Tokyo University of Science)


Publication
Kazutomo Ishi & Fumio Sugawara, Biochemical Pharmacology 75 (2008), 1743-1750 Y. Takakusagi, Y. Kuroiwa, Fumio Sugawara, & K. Sakaguchi, Bioorganic & Medicinal Chemistry 16 (2008), 7410-7414

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