A rational approach for the development of reduced-size analogues of neuropeptide Y with high affinity to the Y1 receptor.
Four sets of centrally truncated analogues of neuropeptide Y have been synthesized. In each series the N-terminal part was constant, while the C-terminal segment was systematically varied in length. The C- and N-terminal parts were linked by 6-aminohexanoic acid. The affinity to the Y1 receptor was investigated on human neuroblastoma cells SK-N-MC. Significant differences were found between the series of peptides as well as within each set. Remarkably, the affinity did not solely depend on the length of the segment, and with increasing numbers of residues the IC50 values were not always decreased. With a given N-terminal segment, only one optimal length of the C-terminal segment was found, which suggests that it is not the amino acids themselves but their 3D arrangement and orientation that is important for high receptor affinity.
Rist
B
B
Department of Pharmacy, ETH Zürich, Switzerland.
Wieland
H A
HA
Willim
K D
KD
Beck-Sickinger
A G
AG
D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*
D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor