Technologies to improve the delivery of peptides represent an attractive strategy to enhance their clinical utility. Development of a novel technology for conjugating amphiphilic oligomers to peptides in order to modulate their pharmacokinetic profile has exciting medical applications. One intriguing possibility is the chemical conjugation of n endogenous appetite-suppressing peptide to facilitate delivery and provide stability. Luminal cholecystokinin releasing factor (LCRF) stimulates the release of cholecystokinin (CCK), a polypeptide hormone that induces satiety and reduces food intake. The aims of this proposal are to: (1) synthesize an LCRF amphiphilic polymer conjugate; (2) assess its ability to release GCK in a cellular assay; and (3) determine its resistance to digestive enzymes. Our laboratory has successfully applied its proprietary conjugation technology to the development of oral insulin and calcitonin. Insulin is now in Phase II clinical trials. Research demonstrating the feasibility of the conjugation technique for successfully modifying key properties of peptides suggests oral delivery of this potent appetite-suppressing peptide will be successful. Once we have optimized the structure of the conjugate, assessed its functional activity, and determined its protease stability, we will proceed to controlled behavioral studies in animals and then humans. PROPOSED COMMERCIAL APPLICATIONS: We propose to optimize the structure and function of a proprietary chemical conjugation technology to facilitate the oral delivery of an endogenous appetite-suppressingn peptide. $30 billion is spent on attempts at weight loss and 55% of the population is overweight or obese. Obesity has grave health consequences including diabetes, heart disease and hypertension. There is a paucity of safe and effective treatments, thus there are significant opportunities for clinical and commercial success for new approaches to weight loss.