Sequential and Environmental Dependence of Conformation in a Small Opioid Peptide.

We report the structural characterization of the μ-selective endogenous opioid endomorphin-1 (EM-1) via an array of nuclear magnetic resonance experiments in both aqueous conditions and, for the first time, in isotropic lipid bicelles, which mimic its endogenous environment. Consistent with computationally derived hypotheses, EM-1 is found to significantly populate a compact, turn-like structure in aqueous solution. This structure is only present as a minor species when the peptide is subjected to a lipid environment, in which the presented NMR data suggests that the major conformer of EM-1 lacks internal hydrogen bonds. The interaction of EM-1 with lipid bilayers is characterized by both tryptophan fluorescence and two-dimensional diffusion ordered NMR spectroscopy; these experiments suggest that the interaction with the surface of phospholipid bilayers, operating as a change in bulk solvation, is responsible for the observed conformational rearrangement in EM-1.