Highly potent and small neuropeptide Y agonist obtained by linking NPY 1–4 via spacer to α‐helical NPY 25–36

Abstract

Analogues of neuropeptide Y (NPY) containing small N- and C-terminal segments linked via flexible spacer arms were found to exhibit receptor binding affinity constants almost as high as NPY as well as post- and presynaptic NPY-agonistic activities. One of the most active analogues contains N-terminal NPY segment 1–4 linked via ε-aminocaproic acid (Aca) to the C-terminal partially α-helical peptide amide segment 25–36. NPY 1–4-Aca-25–36 is the first highly potent NPY agonist, which is of considerably reduced size in comparison to the native hormone. The analogues are accessible by solid-phase synthesis using Fmoc strategy.