Design and Synthesis of γ‐Dipeptide Derivatives with Submicromolar Affinities for Human Somatostatin Receptors

A simple, designed, open-chain γ-dipeptide derivative (see picture; Nap=naphthyl), which contains only three amide bonds, can mimic the 14-amino acid peptide hormone somatostatin. Surprisingly, the highest affinities (KD≈0.5 μM) for human receptors are observed when the “mandatory” Trp and Lys side chains on the turn mimic carry bulky substituents.