Construction and application of H1R ligand screening materials based on SMA stabilization and his-tag covalent immobilization of membrane proteins.
J Chromatogr A
; 1729: 465057, 2024 Aug 16.
Article
em En
| MEDLINE
| ID: mdl-38857565
ABSTRACT
The histamine H1 receptor (H1R) plays a pivotal role in allergy initiation and undergoes the necessity of devising a high-throughput screening approach centered on H1R to screen novel ligands effectively. This study suggests a method employing styrene maleic acid (SMA) extraction and His-tag covalent bonding to immobilize H1R membrane proteins, minimizing the interference of nonspecific proteins interference while preserving native protein structure and maximizing target exposure. This approach was utilized to develop a novel material for high-throughput ligand screening and implemented in cell membrane chromatography (CMC). An H1R-His-SMALPs/CMC model was established and its chromatographic performance (selectivity, specificity and lifespan) validated, demonstrating a significant enhancement in lifespan compared to previous CMC models. Subsequently, this model facilitated high-throughput screening of H1R ligands in the compound library and preliminary activity verification of potential H1R antagonists. Identification of a novel H1R antagonist laid the foundation for further development in this area.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores Histamínicos H1
/
Ensaios de Triagem em Larga Escala
/
Maleatos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article