Synthesis, Characterization and Structure-Activity Studies of a Known Potent Cholecystokinin Octapeptide (CCK-8) Analogue
Hsi, Richard A.
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In 1985, the National Institutes of Health recognized and classified obesity as a disease, According to the New York Academy of Sciences, obesity has been proved to be a reliable indicator for the onset of such problems as heart disease, hypertension, certain cancers, diabetes and diseases of the digestive tract. Obese individuals increase their chances of contracting one or more of these serious health problems by factors ranging from 100 to 1200 percent1 . Although obesity is far from being a "homogeneous" disease with simple, well-defined causes, basic appetite regulation (or lack thereof) may play an important role in contributing to the problems faced by many obese as well as less seriously overweight individuals. The mechanism of appetite regulation is still not well understood, but a model for appetite regulation has been proposed involving several different peptides which may operate as signals to the gastrointestinal tract and central nervous system. One peptide in particular, cholecystokinin octapeptide (CCK -8) , has been studied extensively to determine its role as a physiological mediator of satiety (appetite inhibition)2. Cholecystokinin octapeptide is one of several molecular forms (e.g. CCK-33, CCK-l2, CCK-39) that exist within a family of CCK peptides which have been shown to possess multiple biological activities3 , Cholecystokinin was originally discovered in the intestine as a 33 amino acid residue peptide where it stimulates gastrointestinal mobility and induces both contraction of the gall bladder and release of digestive 4 enzymes from the pancreas. More recently, CCK has been found in the brain where it functions as a neurotransmitterS. The carboxy-terminal octapeptide fragment (CCK 26-33 or CCK-8) is the shortest naturally occurring biologically active fragroent 6 . Today, CCK-8 is known as a potent gastrointestinal hormone and neurotransmitter. It is distributed throughout the central and peripheral nervous systems as well as the gastrointestinal tract. It displays a multitude of biological functions depending upon its location in the body.