Pharmacological properties and biochemical mechanisms of μ-opioid receptor ligands might be due to different binding poses: MD studies
| Autor: | Simone Ronsisvalle, Federica Panarello, Angelo Spadaro, Silvia Franchini, Salvatore Guccione, Matteo Pappalardo, Livia Basile |
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| Rok vydání: | 2020 |
| Předmět: |
Molecular model
medicine.drug_class Allosteric regulation Receptors Opioid mu Pharmacology Molecular Dynamics Simulation Ligands 01 natural sciences 03 medical and health sciences Basal (phylogenetics) Opioid receptor Benzomorphans Drug Discovery medicine Humans allosteric site benzomorphans molecular dynamics molecular modeling MOR opioid receptor orthosteric site 030304 developmental biology 0303 health sciences Binding Sites Molecular Structure Chemistry 0104 chemical sciences Analgesics Opioid 010404 medicinal & biomolecular chemistry Molecular Medicine |
| Zdroj: | Future medicinal chemistry. 12(22) |
| ISSN: | 1756-8927 |
| Popis: | Background: Central and peripheral analgesia without adverse effects relies on the identification of μ-opioid agonists that are able to activate ‘basal’ antinociceptive pathways. Recently developed μ-selective benzomorphan agonists that are not antagonized by naloxone do not activate G-proteins and β-arrestins. Which pathways do μ receptors activate? How can each of them be selectively activated? What role is played by allosteric binding sites? Methodology & results: Molecular modeling studies characterize the amino acid residues involved in the interaction with various classes of endogenous and exogenous ligands and with agonists and antagonists. Conclusions: Critical binding differences between various classes of agonists with different pharmacological profiles have been identified. MML series binding poses may be relevant in the search for an antinociception agent without side effects. |
| Databáze: | OpenAIRE |
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