Cell-Free Protein Labeling for Drug Discovery

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DESCRIPTION (Applicant's abstract): The completion of the human genome project has opened a new chapter in drug discovery. In contrast to conventional methods, where a drug library is screened against a single protein, the entire proteome is now available for screening. However, such drug-proteomic screens are difficult to accomplish using conventional technology because of the need to rapidly convert genome to proteome, engineer specially labeled proteins and screen thousands of samples per hour. This project aims to remove these limitations by screening drug-protein interactions using cell-free expressed labeled proteins and 2-D microarrays. AmberGen will evaluate a series of tags, which are incorporated into proteins during their cell-free expression. Fluorescent tags provide a means to monitor protein expression and detect their interactions with potential drug compounds. Affinity tags provide a means to rapidly isolate cell-free expressed proteins from the cell-free lysate. Drug screens performed on 2-D microarrays of cell-free expressed proteins, reflecting all or part of the human proteome, will be developed which have high sensitivity detection, high throughput and low sample volume requirements. Affymetrix will provide assistance by providing access to their 2-D microarray technology. In Phase II, a proteome on a chip screening system will be developed for sale to pharmaceutical companies. PROPOSED COMMERCIAL APPLICATION: The development of a cell-free based protein expression approach to drug discovery will result in an array of commercial products including reagents and hardware for drug- protoemic screening and an integrated proteome on a chip screening system. AmberGen is currently involved in discussions with companies to form strategic alliances to market these systems. A market which exceeds $2 billion/year is projected for these products.