Abstract
We investigated the binding affinity of new tetrapeptides derived from the C-terminal sequence of CCK8 to central CCKB and peripheral CCKA receptors. Compound 1 (Boc-Trp-Met-Asp-Phe-NH2) showed high affinity for central CCKB receptors (Ki 4.2 x 10(-8) M, pancreas/cortex ratio = 283). Compounds 2 (Suc-Trp-Met-Asp-Phe-NH2) and 3 (Suc-Trp-Leu-Asp-Phe-NH2) also exhibited high affinity (Ki 2.7 x 10(-8) M and 5.6 x 10(-8) M, respectively) but their CCKB selectivity was nearly 50 times higher (Ki ratio greater than 14,000). Replacement of Met or Leu by other amino acids resulted in less effective tetrapeptides.
MeSH terms
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Amino Acid Sequence
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Animals
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Benzodiazepinones / pharmacology
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Cholecystokinin / antagonists & inhibitors
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Cholecystokinin / chemistry
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Cholecystokinin / metabolism*
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Devazepide
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Guinea Pigs
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In Vitro Techniques
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Kinetics
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Molecular Sequence Data
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Pancreas / drug effects
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Pancreas / metabolism
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Peptides / pharmacology
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Phenylurea Compounds*
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Receptors, Cholecystokinin / antagonists & inhibitors
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Receptors, Cholecystokinin / drug effects
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Receptors, Cholecystokinin / metabolism*
Substances
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Benzodiazepinones
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Peptides
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Phenylurea Compounds
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Receptors, Cholecystokinin
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L 365260
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Cholecystokinin
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Devazepide