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Updated: Oct 9, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Design of the Y1-receptor-selective cyclic peptide based on the C-terminal sequence of neuropeptide Y
Y Takebayashi1, H Koga, J Togami
1Lead Discovery Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co Ltd, Ibaraki, Japan. takebaya@yamanouchi.co.jp
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.
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