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Updated: Oct 9, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Structure-affinity relationships of C-terminal cyclic analogue of neuropeptide Y for the Y1-receptor
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 previously reported that a cyclic octapeptide amide, c[D-Cys29, Cys-34]NPY Ac-29-36 (YM-42454) showed a high affinity for Y1-receptors in SK-N-MC cells (Ki=0.047,microM) but not for Y2-receptors in the porcine hippocampus membranes (Ki>10microM). To explore the critical residues of this unique cyclic peptide for Y1-binding activity, the structure-affinity relationships were investigated by means of amino acid replacement. The results indicated that the hydrophobic side-chains of Leu30 and Ile31, the guanidinium groups of Arg33 and Arg33, and the C-terminal amide are critical for the binding affinity of YM-42454 to the Y1-receptor. On the other hand, Thr32 in YM-42454 might not be critical for the Y1-binding affinity. 1H-NMR studies for YM-42454 and its derivatives have suggested that the critical residues are involved in the direct interaction with a Y1-receptor rather than in maintaining the bioactive conformation.
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