Exploring the putative mechanism of allosteric modulations by mixed-action kappa/mu opioid receptor bitopic modulators.
Future Med Chem
; 13(6): 551-573, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33590767
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.
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1
Base de dados:
MEDLINE
Assunto principal:
Receptores Opioides kappa
/
Receptores Opioides mu
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article