Neuropeptide Y: identification of the binding site.
Based on the hypothetical 3D structure of neuropeptide Y (NPY), NPY 1-4-Aca-25-36, a 17 amino acid analogue, has been synthesized replacing the sequence NPY 5-24 by epsilon-aminocaproic acid (Aca). This low-molecular weight deletion analogue showed nearly comparable receptor affinity to NPY. In order to elucidate the structural requirements for receptor recognition each amino acid of 1-4-Aca-25-36 was exchanged by its D-enantiomer, glycine and L-alanine. In addition distinct amino acids were replaced by closely related residues. Multiple peptide synthesis was applied using Fmoc-strategy and BOP activation. Binding assay was performed on rabbit kidney membrane preparations. The results of structure affinity studies suggest that the C-terminal tetrapeptide NPY 33-36 is essential for receptor recognition.
Beck-Sickinger
A G
AG
Institute for Organic Chemistry, University of Tübingen, Germany.
Gaida
W
W
Schnorrenberg
G
G
Lang
R
R
Jung
G
G
D000409:Alanine / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D014644:Genetic Variation; D005998:Glycine / Q000378:metabolism; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D013237:Stereoisomerism
D009478:Neuropeptide Y; D000409:Alanine; D005998:Glycine