Conformational properties of deltorphin: New features of the δ‐opioid receptor

  title={Conformational properties of deltorphin: New features of the $\delta$‐opioid receptor},
  author={Pierandrea Temussi and Delia Picone and Teodorico Tancredi and Roberto Tomatis and Severo Salvadori and Mauro Marastoni and Gianfranco Balboni},
  journal={FEBS Letters},

New insights on μ/δ selectivity of opioid peptides: Conformational analysis of deltorphin analogues

Deltorphins, in fact, are three heptapeptides characterized by a message domain typical of μ‐selective peptides, but endowed of an extremely high δ selectivity, the highest of all natural opioid peptides.

Quantitative two‐dimensional nmr study of dermenkephalin, a highly potent and selective δ‐opioid peptide

The overall data should provide realistic starting models for energy minimization and modelization studies, and the nonuniform values of the temperature coefficient may reflect an equilibrium mixture of folded and extended conformers.

Comparative conformational analyses of μ‐selective dermorphin and §‐selective deltorphin‐II in aqueous solution by 1H‐NMR spectroscopy

Two-dimensional 1H-NMR methods have been used to obtain complete proton resonance assignments and possible solution conformations of dermorphin and deltorphin-II, naturally occurring mu- and delta-selective opioids, respectively, in order to examine the conformational characteristics that are closely related to the selectivities towards mu/delta-opioid receptors.

Folded conformations of the delta-selective opioid dermenkephalin with head-to-tail interactions. A simulated annealing study through NMR restraints.

To examine the conformational characteristics that are related to the selectivity of dermenkephalin towards the delta-receptor, 50 NOE restraints, 7 dihedral angles, and 20 resulting conformers with no severe distance restraint violation were used in simulated annealing and energy minimization procedures.

Asymmetric Synthesis and Conformational Analysis by NMR Spectroscopy and MD of Aba‐ and α‐MeAba‐Containing Dermorphin Analogues

Dermorphin analogues, containing a (S)‐ and (R)‐4‐amino‐1,2,4,5‐tetrahydro‐2‐benzazepin‐3‐one scaffold (Aba) and the α‐methylated analogues as conformationally constrained phenylalanines, were

Opioid activity of dermenkephalin analogues in the guinea‐pig myenteric plexus and the hamster vas deferens

The results obtained emphasise the importance of a negative charge at the C‐terminus of dermenkephalin for selectivity at the δ‐opioid receptor and the role that the d‐configuration plays in determining the bioactive folding of these highly active peptides.

Opioid receptor selectivity reversal in deltorphin tetrapeptide analogues.

Investigation of the structural parameters involved in the delta-opioid selectivity of several families of opioid peptides.

Direct comparison between the biochemical profiles of the [pClPhe4] analogs of the linear constrained peptides and their parent compounds shows that the addition of an electronegative atom on the Phe4 residue of enkephalin sequences is not an absolute parameter for delta-selectivity improvement.

Solution conformations of deltorphin-I obtained from combined use of quantitative 2D-NMR and energy calculations: a comparison with dermenkephalin.

Results suggest that conformational attributes that are common to dermenkephalin and deltorphin-I, i.e., the backbone conformation of the N-terminal tetrapeptide and preferential orientations in the side-chain of Tyr1 (t) and Phe3 (g-) underlie their ability to bind with high selectivity to the delta-opioid receptor.



A 500-MHz proton nuclear magnetic resonance study of mu opioid peptides in a simulated receptor environment.

A family of conformations derived from the NMR data possesses most of the features previously proposed for mu agonists and is fully consistent with an original model of the mu receptor based on the structures of many rigid opiates.

Membrane‐assisted molecular mechanism of neurokinin receptor subtype selection.

Based on the observed membrane structures of substance P, physalaemin, and eledoisin, preferred conformations, orientations and accumulations of 13 mammalian neurokinins and non‐mammalian tachykinins

Proton magnetic resonance studies on dermorphin and its peptide fragments

Comparison of spectroscopic parameters with relative pharmacological activity is proposed as a possible means of studying flexible agonists in solution.

Experimental attempt to simulate receptor site environment. A 500-MHz 1H nuclear magnetic resonance study of enkephalin amides.

The very unusual amide proton chemical shifts and their temperature coefficients suggest the presence of folded conformations in CDCl3 for all peptides, consistent with several models of opioid receptors and with the crystal structure of Leu5-enkephalin.

Molecular mechanism of opioid receptor selection.

The classical site selectivity caused by the receptor requirements for a complementary fit of the agonist to the discriminator site is thus crucially supplemented by a selection mechanism based on peptide membrane interactions (membrane requirements).

Membrane structure of bombesin studied by infrared spectroscopy. Prediction of membrane interactions of gastrin-releasing peptide, neuromedin B, and neuromedin C.

The molecular mechanism of receptor subtype selection by bombesin-like peptides may prove to be similar to that observed earlier for opioid peptides and the neurokinins.

D-alanine in the frog skin peptide dermorphin is derived from L-alanine in the precursor.

A D-alanine-containing peptide termed dermorphin, with potent opiate-like activity, has been isolated from skin of the frog Phyllomedusa sauvagei and the existence of a novel post-translational reaction for the conversion of an L-amino acid to its D-isomer is suggested.

Membrane lipid phase as catalyst for peptide-receptor interactions.

  • D. SargentR. Schwyzer
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1986
In this model a direct ligand-receptor reaction is replaced by multiple sequential steps including surface accumulation of charged ligands, ligand -membrane interactions, and ultimately binding to the receptor itself, and the measured apparent association constant is a function of the whole system rather than just the receptor.