Future medicinal chemistry, 2021-03, Vol.13 (6), p.551-573
2021
Details
- Autor(en) / Beteiligte
- Titel
- Exploring the putative mechanism of allosteric modulations by mixed-action kappa/mu opioid receptor bitopic modulators
- Ist Teil von
- Future medicinal chemistry, 2021-03, Vol.13 (6), p.551-573
- Ort / Verlag
- England: Newlands Press Ltd
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- Taylor & Francis Journals Auto-Holdings Collection
- Beschreibungen/Notizen
- The modulation and selectivity mechanisms of seven mixed-action kappa opioid receptor (KOR)/mu opioid receptor (MOR) bitopic modulators were explored. Molecular modeling results indicated that the ‘message’ moiety of seven bitopic modulators shared the same binding mode with the orthosteric site of the KOR and MOR, whereas the ‘address’ moiety bound with different subdomains of the allosteric site of the KOR and MOR. The ‘address’ moiety of seven bitopic modulators bound to different subdomains of the allosteric site of the KOR and MOR may exhibit distinguishable allosteric modulations to the binding affinity and/or efficacy of the ‘message’ moiety. Moreover, the 3-hydroxy group on the phenolic moiety of the seven bitopic modulators induced selectivity to the KOR over the MOR.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1756-8919eISSN: 1756-8927DOI: 10.4155/fmc-2020-0308Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8027703
- Format
- –
- Schlagworte
- allosteric modulation mechanism, Allosteric Regulation, Allosteric Site, Binding Sites, Humans, kappa opioid receptor (KOR)/mu opioid receptor (MOR), Ligands, mixed-action KOR/MOR ligand, Molecular Docking Simulation, molecular dynamics simulations, Morphinans - chemistry, Morphinans - metabolism, Naltrexone - analogs & derivatives, Naltrexone - chemistry, Naltrexone - metabolism, Protein Binding, psychostimulant abuse and addiction, Receptors, Opioid, kappa - chemistry, Receptors, Opioid, kappa - metabolism, Receptors, Opioid, mu - chemistry, Receptors, Opioid, mu - metabolism, selectivity, Spiro Compounds - chemistry, Spiro Compounds - metabolism, Thermodynamics