4-epianhydrotetracycline and Bacterial-Infections

Genome projects are generating large numbers of potential new targets for drug discovery. One challenge is target validation, proving the usefulness of a specific target in an animal model. In this paper, we demonstrate a new approach to validation and assay development. We selected in vitro specific peptide binders to a potential pathogen target. By inducing the expression of a selected peptide in pathogen cells causing a lethal infection in mice, the animals were rescued. Thus, by combining in vitro selection methods for peptide binders with inducible expression in animals, the target's validity was rigorously tested and demonstrated. This approach to validation can be generalized and has the potential to become a valuable tool in the drug discovery process.

Topics: Amino Acid Sequence; Amino Acyl-tRNA Synthetases; Animals; Bacterial Infections; Bacteriophages; Disease Models, Animal; Drug Design; Escherichia coli; Gene Expression; Gene Expression Regulation; Gene Transfer Techniques; Glutathione Transferase; Mice; Molecular Sequence Data; Oligopeptides; Peptide Library; Protein Binding; Recombinant Fusion Proteins; Survival Rate; Tetracyclines