Steric interactions and the activity of fentanyl analogs at the mu-opioid receptor
Само за регистроване кориснике
2006
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 p-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 ident...ified as being important for ligand binding or receptor activation: Ile322, Gly325, Val300, Met203, Leu200, Val143, and Ile144. (c) 2005 Elsevier Ltd. All rights reserved.
Кључне речи:
molecural modeling / fentanyl analogs / ligand-receptor interactions / docking simulationИзвор:
Bioorganic and Medicinal Chemistry, 2006, 14, 9, 2887-2895Издавач:
- Pergamon-Elsevier Science Ltd, Oxford
DOI: 10.1016/j.bmc.2005.12.010
ISSN: 0968-0896
PubMed: 16376082
WoS: 000236591200002
Scopus: 2-s2.0-33644982587
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Došen-Mićović, Ljiljana AU - Ivanović, Milovan AU - Micovic, V PY - 2006 UR - https://cherry.chem.bg.ac.rs/handle/123456789/771 AB - 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 p-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. (c) 2005 Elsevier Ltd. All rights reserved. PB - Pergamon-Elsevier Science Ltd, Oxford T2 - Bioorganic and Medicinal Chemistry T1 - Steric interactions and the activity of fentanyl analogs at the mu-opioid receptor VL - 14 IS - 9 SP - 2887 EP - 2895 DO - 10.1016/j.bmc.2005.12.010 ER -
@article{ author = "Došen-Mićović, Ljiljana and Ivanović, Milovan and Micovic, V", year = "2006", 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 p-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. (c) 2005 Elsevier Ltd. All rights reserved.", publisher = "Pergamon-Elsevier Science Ltd, Oxford", journal = "Bioorganic and Medicinal Chemistry", title = "Steric interactions and the activity of fentanyl analogs at the mu-opioid receptor", volume = "14", number = "9", pages = "2887-2895", doi = "10.1016/j.bmc.2005.12.010" }
Došen-Mićović, L., Ivanović, M.,& Micovic, V.. (2006). Steric interactions and the activity of fentanyl analogs at the mu-opioid receptor. in Bioorganic and Medicinal Chemistry Pergamon-Elsevier Science Ltd, Oxford., 14(9), 2887-2895. https://doi.org/10.1016/j.bmc.2005.12.010
Došen-Mićović L, Ivanović M, Micovic V. Steric interactions and the activity of fentanyl analogs at the mu-opioid receptor. in Bioorganic and Medicinal Chemistry. 2006;14(9):2887-2895. doi:10.1016/j.bmc.2005.12.010 .
Došen-Mićović, Ljiljana, Ivanović, Milovan, Micovic, V, "Steric interactions and the activity of fentanyl analogs at the mu-opioid receptor" in Bioorganic and Medicinal Chemistry, 14, no. 9 (2006):2887-2895, https://doi.org/10.1016/j.bmc.2005.12.010 . .