TY - JOUR T1 - Structure-activity relationship of novel pentapeptide neuropeptide Y receptor antagonists is consistent with a noncontinuous epitope for ligand-receptor binding. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 425 LP - 432 VL - 48 IS - 3 AU - A J Daniels AU - J E Matthews AU - O H Viveros AU - J J Leban AU - M Cory AU - D Heyer Y1 - 1995/09/01 UR - http://molpharm.aspetjournals.org/content/48/3/425.abstract N2 - We report the first systematic study on short peptide structure affinity and activity for the neuropeptide Y (NPY) receptor. A series of linear pentapeptides has been synthesized that display affinities in the low micromolar range toward rat brain NPY receptors. Furthermore, some of these compounds competitively antagonize the Y1-type NPY receptor-mediated increase in cytosolic Ca2+ in human erythroleukemic (HEL) cells. The inactive NPY carboxyl-terminal pentapeptide (Thr-Arg-Gln-Arg-Tyr-NH2; IC50 > 100 microM) was modified by replacing threonine with an aromatic amino acid and glutamine with leucine. This resulted in a series of pentapeptides with dramatically improved affinity (IC50 = 0.5-4 microM) for the rat brain receptor. The structure-affinity data suggest that these peptides may represent a noncontinuous epitope containing the amino-terminal tyrosine and the carboxyl-terminal residues Arg-35 and Tyr-36 of NPY. ER -