CHOLECYSTOKININ ANALOGUES

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The syntheses of 19 cholecystokinin-octapeptide analogues are proposed. The preparation of these peptides will involve solid-phase techniques and purification on a new instrument for counter-current chromatography, the horizontal flow-through coil planet centrifuge. The binding of these peptides to cholecystokinin central nervous system and pancreatic receptors will be determined. Additionally, the peptides will be screened for either agonist activity or antagonism in animal behavior paradigms and in guinea pig pancreatic acinar cell secretion. Thus, potential centrally, behaviorally and physiologically active peptides, suitable for the study of cholecystokinin function will be identified. The peptides are to be made available for research in food-related behaviors and pre-clinical research in areas relating to neurological and gastrointestinal diseases. Methods to prepare large amounts of the most active peptides are proposed to be developed. These include modification of the chemical synthetic procedure and use of a preparative-scale coil planet centrifuge to be custom built for this purpose.