NMR studies of a series of dehydrodermorphins.
The third and fifth aromatic residues of dermorphin, a potent mu-opioid peptide, and of its N-terminal fragments, from the pentapeptide to the parent heptapeptide amide, have been systematically substituted with Z-dehydrophenylalanine (delta-Phe) and/or Phe to investigate the conformation-activity relationship. The characterization in DMSO-d6 at 500 MHz indicates that, in this solvent, all peptides adopt essentially random, extended conformations, as a consequence of the strong solvation. The chemical shift of the methyl group of D-Ala is influenced by the precise orientation of the side chain of the third residue in a fashion that can be correlated to the mu potency, consistently with our model of mu-receptor. However, the complexes of the pentapeptides with 18-crown-6-ether, when dissolved in chloroform, adopt ordered, folded conformations, a behavior that closely parallels the CD observations in methanol.
Castiglione-Morelli
M A
MA
Saviano
G
G
Temussi
P A
PA
Balboni
G
G
Salvadori
S
S
Tomatis
R
R
D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides; D018847:Opioid Peptides; D011487:Protein Conformation
D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin