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 14 linked via e-aminocaproic acid (Aca) to the C-terminal partially a-helical peptide amide segment 25-36. NPY 14Aca-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.
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