Structure–activity relationships of neuropeptide Y analogues with respect to Y 1 and Y 2 receptors

Secondary structure investigations, affinities, and activities of neuropeptide Y analogues with respect to the Y 1 and the Y 2 receptor are reviewed. The results are discussed with respect to the different prerequisites for affinities to both receptor subtypes. The results from a systematic scanning of the hormone using L ‐alanine and from a large variety of discontinuous and cyclic analogs suggest that two different conformations of neuropeptide Y are adopted at the Y 1 and Y 2 receptors. Whereas a C‐terminal turn structure is suggested for Y 1 receptor affinity, an α‐helical conformation of the C‐terminus is afforded for good binding to the Y 2 receptor. © 1994 John Wiley & Sons, Inc.