This proposal represents a request for an RSDA to support my career development in the area of opioid peptide biosynthesis. Active opioid peptides, like other neuropeptides and hormones, are formed through the action of intracellular processing enzymes which cleave and then modify precursor proteins. This proposal addresses the specific proteolytic mechanisms resulting in opioid peptide formation. Since the biochemical basis for the addictive properties of opiate drugs may relate to deficiencies in the biosynthetic capacity for opiold peptides, a thorough understanding of key regulatory enzymes has potential relevance to the rational design of enzyme-based drugs serving as therapeutic agents in opiate addiction. My short-term goals are to describe the interaction of the newly discovered PC processing enzymes with proenkephalin, both in vitro and in cells. My long-term objectives are to understand the cell biology, biochemistry, and turnover of opioid peptides.