Controlling the selectivity of aminergic GPCR ligands from the extracellular vestibule.
Bitopic ligand
Fragment linking
GPCR
Secondary binding pocket
Selectivity
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
26
10
2020
revised:
18
01
2021
accepted:
15
03
2021
pubmed:
8
4
2021
medline:
15
10
2021
entrez:
7
4
2021
Statut:
ppublish
Résumé
In addition to the orthosteric binding pocket (OBP) of GPCRs, recent structural studies have revealed that there are several allosteric sites available for pharmacological intervention. The secondary binding pocket (SBP) of aminergic GPCRs is located in the extracellular vestibule of these receptors, and it has been suggested to be a potential selectivity pocket for bitopic ligands. Here, we applied a virtual screening protocol based on fragment docking to the SBP of the orthosteric ligand-receptor complex. This strategy was employed for a number of aminergic receptors. First, we designed dopamine D
Identifiants
pubmed: 33826962
pii: S0045-2068(21)00209-1
doi: 10.1016/j.bioorg.2021.104832
pii:
doi:
Substances chimiques
Ligands
0
Pyrimidinones
0
Receptors, G-Protein-Coupled
0
Urea
8W8T17847W
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104832Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.