Influence of solvent and configuration of residues at positions 2 and 3 on distance and mobility of pharmacophore groups at positions 1 and 4 in cyclic enkephalin analogues

Abstract

The analgesic activity of opioid peptides is mainly connected with their affinity and selectivity for the μ-receptors. The biological activity of cyclic opioid analogues depends on mutual orientation and conformational freedom of aromatic pharmacophore groups at positions 1 and 4. The distance and distance distributions between chromophores at positions 1 [Phe(p-NO2), p-nitrophenylalanine] and 4 [Nal, β-(2-naphthyl)alanine], which constitute an energy donor–acceptor pair, were calculated based on measured fluorescence intensity decays of a donor (Nal). The influence of the solvent and configuration of the residues at position 2 and 3 on donor–acceptor distance distribution and mobility of pharmacophore groups at position 1 and 4 in cyclic enkephalin analogues are discussed. © 2001 John Wiley & Sons, Inc. Biopolymers 59: 180–190, 2001