Pharmacological properties and biochemical mechanisms of μ-opioid receptor ligands might be due to different binding poses : MD studies
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Future medicinal chemistry - 12(2020), 22 vom: 24. Nov., Seite 2001-2018 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ronsisvalle, Simone [VerfasserIn] |
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| Links: |
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| Themen: |
Allosteric site |
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| Anmerkungen: |
Date Completed 02.08.2021 Date Revised 02.08.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2020-0249 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31543063X |
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| 100 | 1 | |a Ronsisvalle, Simone |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacological properties and biochemical mechanisms of μ-opioid receptor ligands might be due to different binding poses |b MD studies |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 02.08.2021 | ||
| 500 | |a Date Revised 02.08.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a MOR | |
| 650 | 4 | |a allosteric site | |
| 650 | 4 | |a benzomorphans | |
| 650 | 4 | |a molecular dynamics | |
| 650 | 4 | |a molecular modeling | |
| 650 | 4 | |a opioid receptor | |
| 650 | 4 | |a orthosteric site | |
| 650 | 7 | |a Analgesics, Opioid |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a Receptors, Opioid, mu |2 NLM | |
| 700 | 1 | |a Panarello, Federica |e verfasserin |4 aut | |
| 700 | 1 | |a Spadaro, Angelo |e verfasserin |4 aut | |
| 700 | 1 | |a Franchini, Silvia |e verfasserin |4 aut | |
| 700 | 1 | |a Pappalardo, Matteo |e verfasserin |4 aut | |
| 700 | 1 | |a Guccione, Salvatore |e verfasserin |4 aut | |
| 700 | 1 | |a Basile, Livia |e verfasserin |4 aut | |
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