| abstract |
The invention provides a cytotoxicity-based genetic selection (TOXSEL) method and related testing kit for the identification and positive selection of molecules or mutations that are capable of disrupting a specific protein-protein interaction. The invention enables positive selection of molecules disruptive of specific protein-protein interactions by virtue of the presence in the TOXSEL system of a toxin reporter gene. A disrupted protein-protein interaction precludes expression of the toxin reporter gene and, consequently, allows survival of the host cell. TOXSEL technology enables large-scale screening for drugs or small molecules capable of disrupting specific protein-protein interactions critical in processes such as cellular signalling, carcinogenesis, etc. The positive selection of molecules or mutations capable of interfering with specific protein-protein interactions permits the identification of amino acid residues or motifs critical in the protein-protein interactions and permits the design of drugs for therapeutic or diagnostic applications. |