(104f) Directed Evolution of Structured Peptides

Small peptides (10-20 amino acids) are frequently unstructured in solution. Although a few examples of structured peptides exist, these are generally limited to peptides with known β-turn motifs. We have developed a selection scheme for the directed evolution of novel peptides that are structured in solution. Our selection scheme ? proteolytic release of immobililzed phage (PRIP) ? is based on the resistance to proteolytic release of immobilized filamentous bacteriophage displaying peptides of interest on their surface. We are currently using PRIP to isolate peptides that exhibit structure in response to specific environmental stimuli ? such as the presence of a soluble small molecule ? by selecting for structured peptides in the presence of the stimulus (positive selection), followed by selection of unstructured peptides in the absence of the stimulus (negative selection). PRIP-derived stimuli-responsive peptides can be used to create ?smart' biomaterials. Structured peptides identified using PRIP also have the potential to supply new proteolytically resistant scaffolds for the creation of peptide drugs.