CCK-8-related C-terminal tetrapeptides: affinities for central CCKB and peripheral CCKA receptors.
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.
Harhammer
R
R
Institute of Pharmacology and Toxicology, Humboldt University of Berlin, F.R.G.
Schäfer
U
U
Henklein
P
P
Ott
T
T
Repke
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D020109:Devazepide; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*
D001570:Benzodiazepinones; D010455:Peptides; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; D020109:Devazepide