SELECTION OF RECEPTOR-BINDING PEPTIDES FROM MIXTURES

THIS PROJECT DESCRIBES AN APPROACH TO FACILITATE THE DISCOVERY OF PEPTIDE-BASED RECEPTOR AGONISTS/ANTAGONISTS OR ENZYME INHIBITORS. IN THIS APPROACH, RECEPTORS AND ENZYMES ARE USED AS AFFINITY REAGENTS TO SELECT TIGHTLY BINDING PEPTIDES FROM EQUIMOLAR MIXTURES OF SYNTHETIC PEPTIDES. PROTOS CORPORATION HAS ALREADY DEVELOPED METHODS FOR THE CONTROLLED SYNTHESIS OF PEPTID MIXTURES. THE STRUCTURES OFTHESE BOUND PEPTIDES WILL BE DETERMINED BY A COMBINATION OF ANALYTICAL TECHNIQUES. A MODEL SYSTEM, CONSISTING OF A MONOCLONAL ANTIBODY OF KNOWN SPECIFICITY, WILL BE USED TO TEST THE FEASIBILITY OF THIS BIOCHEMICAL SELECTION APPROACH. AN AFFINITY COLUMN WITH THE ANTIBODY WILL BE USEDTO SELECT TIGHTLY BINDING PEPTIDES FROM AN EQUIMOLAR MIXTUREOF PEPTIDES, AND THE BOUND PEPTIDE OR PEPTIDES WILL BE CHARACTERIZED. THE LONG-TERM GOAL IS TO DEVELOP GENERIC METHODS THAT WILL ALLOW THE RAPID DISCOVERY OF PEPTIDES THAT BIND TIGHTLY TO PROTEIN RECEPTORS, ENZYMES, OR ANTIBODIES. THESE TIGHTLY BINDING PEPTIDES WILL THEN SERVE AS LEAD COMPOUNDS FOR THE DEVELOPMENT OF NEW THERAPEUTIC AGENTS.