Design of the Y1-receptor-selective cyclic peptide based on the C-terminal sequence of neuropeptide Y

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Abstract
We designed four cyclic peptides which are mimics of the C‐terminal region of human neuropeptide Y (NPY) on the basis of the structural model of NPY. One of these cyclic peptides, c[D‐Cys29‐L‐Cys34]NPY Ac‐29‐36 (YM‐42454), exhibited significantly higher affinity for the Y1‐receptor than the corresponding C‐terminal linear fragment, NPY Ac‐28‐36. Interestingly, YM‐42454 showed binding affinity for the Y1‐receptor in spite of the lack of the N‐terminal sequence of NPY, whereas it did not show any binding affinity for the Y2‐receptor. This conformationally restricted Y1‐selective peptide would provide some insights into the bioactive conformation of the C‐terminal region of NPY.