Development of a Common 3D Pharmacophore for delta-Opioid Recognition from Peptides and Non-Peptides Using a Novel Computer Program

Ping Huang, Susan Kim, and Gilda H. Loew

J. Comp.-Aided Mol. Design 11: 21-27 (1997).

Abstract

A unified three-dimensional (3D) pharmacophore for recognition of the delta-opioid receptor by families of structurally diverse delta-opioid ligands, including peptides and non-peptides, has been determined. An additional structural feature required for delta-selectivity was also characterized using a subset of these ligands that are highly selective for the delta-opioid receptor. To obtain these pharmacophores, we have used a recently developed computer program that performs systematic and automated comparisons of molecules to determine whether any common 3D relationships exist among candidate recognition moieties in high- affinity analogs. All the low-energy conformations of each ligand are included in these comparisons. The program developed should be applicable in general to molecular super- imposition problems in rational drug design and to develop both 3D recognition and activation pharmacophores for any receptor for which high- and low-affinity analogs and agonists and antagonists have been identified. Copyright © 1997 ESCOM Science Publishers B.V.