Structure–activity relationships of neuropeptide Y analogues with respect to Y1 and Y2 receptors

Secondary structure investigations, affinities, and activities of neuropeptide Y analogues with respect to the Y₁ and the Y₂ 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 Y₁ and Y₂ receptors. Whereas a C-terminal turn structure is suggested for Y₁ receptor affinity, an α-helical conformation of the C-terminus is afforded for good binding to the Y₂ receptor. © 1994 John Wiley & Sons, Inc.