Premium
Topographical requirements for δ‐selective opioid peptides
Author(s) -
Nikiforovich Gregory V.,
Hruby Victor J.,
Prakash Om,
Gehrig Catherine A.
Publication year - 1991
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.360310804
Subject(s) - conformational isomerism , chemistry , side chain , stereochemistry , opioid peptide , position (finance) , amino acid , opioid , molecule , receptor , biochemistry , organic chemistry , finance , economics , polymer
The conformational possibilities of three different δ‐selective opioid peptides, which are DPDPE, and DRE (Tyr‐ D ‐Met‐Phe‐His‐Leu‐Met‐Asp‐NH 2 , dermenkephalin), were explored using energy calculations. Sets of low‐energy conformers were obtained for each of these peptides. The sets consisted of 61 structures for DPDPE, 32 for DCFPE, and 38 for DRE, including various types of rotamers of the Tyr and Phe side‐chain groups. Comparison of the geometrical shapes of the conformers was performed for these sets using topographical considerations, i.e., examination of the mutual spatial arrangement of the N‐terminal α‐amino group, and of the Tyr and Phe side‐chain groups. The results obtained suggest a model for the δ‐receptor‐bound conformer(s) for opioid peptides. The model suggests the placement of the Phe side chain in a definite position in space corresponding to the g − rotamer of Phe for peptides containing Phe 4 and to the t rotamer for peptides containing Phe. 3 The position of the Tyr 1 side chain cannot be specified so precisely. The proposed model is in a good agreement with the results of biological testing of β‐Me‐Phe 4 ‐substituted DPDPE analogues that were not considered in the process of model construction.