Design of the Y1-receptor-selective cyclic peptide based on the C-terminal sequence of neuropeptide Y.
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.
Takebayashi
Y
Y
Lead Discovery Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co Ltd, Ibaraki, Japan. takebaya@yamanouchi.co.jp
Koga
H
H
Togami
J
J
Inui
A
A
Kurihara
H
H
Koshiya
K
K
Furuya
T
T
Tanaka
A
A
Murase
K
K
D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009478:Neuropeptide Y / Q000737:chemistry*; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013552:Swine; D014407:Tumor Cells, Cultured
D009478:Neuropeptide Y; D010455:Peptides