title: The mu-selective heptapeptide opioid dermorphin has two conformations around Phe3 psi with no head-to-tail interaction. A quantitative 2-D NMR and molecular modeling analysis.
abstract: The mu opioid heptapeptide Dermorphin (DRM) is under 70 % of trans forms for the Tyr(5)-Pro(6) peptide bond in solution (CDCl(3)/DMSO-d(6) 1/1 vol/vol). Variations of NOE integrals at 5 temperatures show apparent correlation times of 0.8 to 0.9 ns (at 280 K) in that mixed solvent. Four NOE between non-adjacent residues reveal a large population of folded structures. However, in trans DRM, 4 adjacent NOE Phe(3)/Gly(4) can only be explained by an equilibrium between folded (psi(3) > 0) and extended (psi(3) > 0) conformations. Simulated annealing modeling gave about 60% (psi(3) > 0) and 40% (psi(3) > 0) of these conformer populations. Trans DRM study and previous studies on the heptapeptide opioids, dermenkephalin (DREK) and deltorphin-I (delta selective), and DREK(1-4)-DRM(5-7) hybrid (mu selective), show in folded structures more backbone bending of the first 4 residues in the mu opioids than in the delta peptides. Also, the main difference between mu- and delta-opioid peptides is a large fraction of extended conformations in mu heptapeptides. Either bending of the N-terminus, or extension of the C-terminal part in mu-opioid heptapeptides prevent the head-to-tail interactions which allow delta-opioid peptides to bind selectively to the delta-opioid receptor.
authors.affiliation: Laboratoire de Dynamique, Interactions et Réactivité UMR 7075,(CNRS-Université Paris 6), CNRS, 2 rue H. Dunant, 94320 Thiais, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Riand
authors.forename: Pierre
authors.initials: P
authors.lastname: Nicolas
authors.forename: Daniel
authors.initials: D
authors.lastname: Baron
mesh_terms: D000595:Amino Acid Sequence; D000663:Amphibians; D000818:Animals; D006860:Hydrogen Bonding; D007536:Isomerism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D018847:Opioid Peptides; D011487:Protein Conformation; D017510:Protein Folding; D011522:Protons; D012996:Solutions; D013696:Temperature
chemical_list: D009842:Oligopeptides; D018847:Opioid Peptides; D011522:Protons; D012996:Solutions; C030058:dermorphin