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 CCK(B) and peripheral CCK(A) receptors. Compound 1 (Boc-Trp-Met-Asp-Phe-NH2) showed high affinity for central CCK(B) receptors (K(i) 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 (K(i) 2.7 X 10(-8) M and 5.6 x 10(-8) M, respectively) but their CCK(B) selectivity was nearly 50 times higher (K(i)(ratio > 14000). Replacement of Met or Leu by other amino acids resulted in less effective tetrapeptides.