| Literature DB >> 33590767 |
Huiqun Wang1, Danni Cao2, James C Gillespie3, Rolando E Mendez3, Dana E Selley3, Lee-Yuan Liu-Chen2, Yan Zhang1.
Abstract
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.Entities:
Keywords: allosteric modulation mechanism; kappa opioid receptor (KOR)/mu opioid receptor (MOR); mixed-action KOR/MOR ligand; molecular dynamics simulations; psychostimulant abuse and addiction; selectivity
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Year: 2021 PMID： 33590767 PMCID： PMC8027703 DOI： 10.4155/fmc-2020-0308
Source DB: PubMed Journal: Future Med Chem ISSN： 1756-8919 Impact factor: 3.808