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

Further Evidence for the Absence of Polyproline II Stretch in the XAO Peptide

“…As nice as the idea of well-defined conformations of peptides might appear, one must be cautious about assuming that a linear peptide has a stable conformation even at low temperatures. A wealth of experimental data (e.g., fluorescence quenching (24)(25)(26)) suggests that the distances between residues are broadly distributed rather than being focused. It should, therefore, at least be considered that the observables measured for XAO and other alanine-based peptides are conformational averages rather than being indicative of specific conformation(s).…”