Title:Molecular Docking of Opiates and Opioid Peptides, a Tool for the Design of Selective Agonists and Antagonists, and for the Investigation of Atypical Ligand-Receptor Interactions
VOLUME: 19 ISSUE: 11
Author(s):L. Gentilucci, A. Tolomelli, R. De Marco and R. Artali
Affiliation:Department of Chemistry “G. Ciamician“, University of Bologna, via Selmi 2, 40126, Bologna, Italy.
Keywords:Opioid receptors, peptides, morphine, fentanyl, endomorphin, molecular docking, salvinorin, D-Trp-Phe, JOM, conformational
analysis, ligand-receptor interactions, GPCR
Abstract:In the last years, molecular docking emerged as a powerful tool to investigate the interactions between opioid ligands and their
receptors, thus driving the design and development of new selective agonists or antagonists of therapeutic interest. This review especially
covers the most representative and recent comparative molecular docking analyses of structurally related compounds, as well as of
agonists and antagonists within the active and inactive states of the receptors. The comparative analyses gave important information on
the structural determinants responsible for the affinity and selectivity of the ligands, and defined the features responsible for the
activation of the receptors. A special section is dedicated to the analyses of recently discovered, unusual agonists lacking of the tyramine
pharmacophore, such as Salvinorin A, and the cyclopeptides which comprise the D-Trp-Phe pharmacophoric motif. For the atypical
structure of these compounds, the docking proved to be essential to disclose how they interact with and activate the receptors.
