Steric interactions and the activity of fentanyl analogs at the mu-opioid receptor.
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Dosen-Micovic L, Ivanovic M, Micovic V
Steric interactions and the activity of fentanyl analogs at the mu-opioid receptor.
Bioorg Med Chem. 2006 May 1;14(9):2887-95. Epub 2006 Jan 11.
- PubMed ID
- 16376082 [ View in PubMed]
- Abstract
Fentanyl is a highly potent and clinically widely used narcotic analgesic. The synthesis of its analogs remains a challenge in the attempt to develop highly selective mu-opioid receptor agonists with specific pharmacological properties. In this paper, the use of flexible molecular docking in a study of the formation of complexes between a series of active fentanyl analogs and the mu-opioid receptor is described. The optimal position and orientation of fourteen fentanyl analogs in the binding pocket of the mu-receptor were determined. The major receptor amino acids and the ligand functional groups participating in the complex formation were identified. Stereochemical effects on the potency and binding are explained. The proposed model of ligand-receptor binding is in agreement with point mutation experiments explaining the role of the amino acids: Asp147, Tyr148, Asn230, His297, Trp318, His319, Cys321, and Tyr326 in the complex formation. In addition, the following amino acids were identified as being important for ligand binding or receptor activation: Ile322, Gly325, Val300, Met203, Leu200, Val143, and Ile144.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions 3-Methylthiofentanyl Mu-type opioid receptor Protein Humans YesAgonistDetails Fentanyl Mu-type opioid receptor Protein Humans YesAgonistDetails