Premium
Quantitative two‐dimensional nmr study of dermenkephalin, a highly potent and selective δ‐opioid peptide
Author(s) -
Naim Mohammed,
Charpentier Stéphane,
Nicolas Pierre,
Baron Daniel
Publication year - 1993
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360331214
Subject(s) - chemistry , conformational isomerism , two dimensional nuclear magnetic resonance spectroscopy , dihedral angle , nuclear magnetic resonance spectroscopy , nuclear overhauser effect , amide , geminal , coupling constant , spectroscopy , crystallography , j coupling , peptide , stereochemistry , hydrogen bond , side chain , molecule , organic chemistry , physics , biochemistry , particle physics , quantum mechanics , polymer
Dermenkephalin, H‐Tyr‐( D ) Met‐Phe‐His‐Leu‐Met‐Asp‐NH 2 , a highly potent and selective δ‐opioid peptide isolated from frog skin, was studied in DMSO‐d 6 solution by two‐dimensional nmr spectroscopy, including the determination of NH temperature coefficients, the evaluation of 3 J coupling constants from phase‐sensitive correlated spectroscopy (COSY) and the volumes of nuclear Overhauser effect (NOE) correlations. The two‐dimensional NOE spectroscopy (NOESY) spectrum of dermenkephalin revealed sequential, medium‐, and long‐range effects. To put this information on a quantitative basis, special attention was devoted to J cross‐peak suppression, quantification of the NOE volumes and analysis of the overlaps, normalization of the NOEs against diagonal peaks and H ββ′ geminal interactions. Although most of the dihedral angles deduced from the 3 J Nα coupling constants together with several N i α i and α i N i + 1 NOEs pointed to a partially extended peptide backbone, several N i N i + 1 NOEs and β i N i + 1 interactions argued in favor of a folded structure. Moreover, several long‐range correlations of strong intensities were found that supported a close spatial proximity between the side chains of D ‐Met 2 and Met 6 , Tyr 1 and His 4 , Tyr 1 and Asp 7 , and His 4 and the C‐terminal amide group. In Phe, the g − rotamer in the side chain is deduced from the 3 J αβ coupling constants and αβ and Nβ NOE correlations. Whereas the amide proton dependency was not indicative of stable hydrogen bonds, the nonuniform values of the temperature coefficient may reflect an equilibrium mixture of folded and extended conformers. The overall data should provide realistic starting models for energy minimization and modelization studies. © 1993 John Wiley & Sons, Inc.