Studies on the structural requirement for ligand binding to the neuropeptide Y (NPY) receptor from rat cerebral...

Analogues of the NPY model peptide NPY 1-4-Aca-25-36 were synthesized by solid phase peptide synthesis using the tea-bag method for parallel peptide synthesis. The affinity of the peptides as ligands to the NPY receptor in rat cerebral cortex was investigated. The model compound NPY 1-4-Aca-25-36 was a relatively poor ligand to the NPY receptor in rat brain (IC50 = 0.40 microM). Arg35 and Arg33 were both important for ligand recognition by the NPY receptor. Substitutions in several positions in the region corresponding to the C-terminal part of NPY resulted in analogues with only minor reduction of the affinity for the NPY receptor.