INNOVATIVE METHODS FOR PREPARATION OF OPIOID PEPTIDES

THE OBJECTIVE OF THIS PROPOSAL IS TO DEVELOP PRACTICAL METHODS FOR THE PRODUCTION OF OPIOID PEPTIDES. SIGNIFICANT PROGRESS IN OPIOID PEPTIDE RESEARCH HAS BEEN ACHIEVED IN THEAREAS OF LABORATORY SYNTHESIS, PURIFICATION, AND CHEMICAL & BIOLOGICAL ANALYSIS. STUDY OF RECEPTOR SPECIFIC OPIOID LIGANDS HAS POTENTIAL TO LEAD TO NONADDICTIVE ANALGESICS. THE IMPORTANCE OF RESEARCH AND DEVELOPMENT IN THIS FIELD IS UNDERSCORED BY THE SUPPORT PROVIDED BY NIDA TO NUMEROUS INVESTIGATORS. ONE OF THE GOALS OF THE CURRENT PROPOSAL IS TO OFFER CHEMICALLY AND OPTICALLY PURE OPIOID PEPTIDES TO ASSIST NIDA IN THIS EFFORT. A NUMBER OF PEPTIDE SYNTHESIS PROCEDURES - BOTH SOLID PHASE AND HOMOGENEOUS SOLUTION WILL BE EVALUATED DURING THE PHASE I STUDY IN ORDER TO DEVELOP METHODS SUITABLE FOR PREPARING MULTIGRAM QUANTITIES OF PEPTIDES. PRACTICAL TECHNIQUES FOR LARGE-SCALE PURIFICATION OF SYNTHETIC PEPTIDES WILL ALSO BE STUDIED. PEPTIDES PREPARED IN THIS STUDY WILL BE CAREFULLY ANALYZED BY ANALYTICAL METHODS INCLUDING HPLC. THESE PROCEDURES WILL BE APPLIED TO THE SYNTHESIS OF THREE DELTA-SELECTIVE ENKEPHALIN ANALOGS, ONE MU-SELECTIVE MORPHICEPTIN, AND FOUR DYNORPHIN PEPTIDES. SAMPLES OF ALL PEPTIDES PREPARED DURING THIS STUDY WILL BE PROVIDED TO NIDA. IN A FUTURE INVESTIGATION, METHODS DEVELOPED IN THIS STUDY COULD BE APPLIED TO THE PRODUCTION OF BIOLOGICALLY ACTIVE PEPTIDES IN KILOGRAM QUANTITIES.