Development of fast screening methods for toxicological mode of actions with phage display

New EU regulations raise the need for fast screening methods that can be used for the characterization of chemicals. The prediction of the mechanisms of toxicity of a compound is crucial for its characterization. A factor that can be used for this purposes is the cellular protein target. This is the protein with which the chemical compound initially interacts and that is responsible for further toxic effects. In this study, cDNA-phage display is used to develop an assay for determining the cellular target of a compound. Cellular proteins are displayed on phage membrane protein VI, by fusing human cDNA library to M13 filamentous phage gene VI. The affinity of a compound for phages that are displaying a cellular target, allows for the prediction of the mechanism of toxicity. The affinity of a phage for a compound makes it possible to predict if the compound interacts with the cellular protein and to assess its toxic potency.