CCK-8-related C-terminal tetrapeptides: affinities for central CCK B and peripheral CCK A receptors

Abstract

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NH 2) showed high affinity for central CCK B receptors (K i4.2×10 −8 M, pancreas/cortex ratio = 283). Compounds 2 (SucTrpMetAspPheNH 2) and 3 (SucTrpLeuAspPheNH 2) also exhibited high affinity (K i 2.7 × 10 −8 M and 5.6 × 10 −8 M, respectively) but their CCK B selectivity was nearly 50 times higher (K i ratio > 14 000). Replacement of Met or leu by other amino acids resulted in less effective tetrapeptides.