Gallate Moiety of Catechin Is Essential for Inhibiting CCL2 Chemokine-Mediated Monocyte Recruitment.
J Agric Food Chem
; 71(12): 4990-5005, 2023 Mar 29.
Article
en En
| MEDLINE
| ID: mdl-36942659
ABSTRACT
Leukocyte recruitment witnesses an orchestrated complex formation between the chemokines and their molecular partners. CCL2 chemokine that regulates monocyte trafficking is a worthwhile system from the pharmaceutical perspective. In the current study, four major catechins (EC/EGC/ECG/EGCG) were assessed for their inhibitory potential against CCL2-regulated monocyte/macrophage recruitment. Interestingly, catechins with the gallate moiety (ECG/EGCG) could only attenuate the CCL2-induced macrophage migration. These molecules specifically bound to CCL2 on a pocket comprising the N-terminal, ß0-sheets, and ß3-sheets, and the binding affinity of ECGC (Kd = 22 ± 4 µM) is â¼4 times higher than that of the ECG complex (Kd = 85 ± 6 µM). MD simulation analysis evidenced that the molecular specificity/stability of CCL2-catechin complexes is regulated by multiple factors, including stereospecificity, number of hydroxyl groups on the annular ring-B, the positioning of the carbonyl group, and the methylation of the galloyl ring. Further, a significant overlap on the binding surface of CCL2 for EGCG/ECG and receptor interactions as evidenced from NMR data provided the rationale for the observed inhibition of macrophage migration in response to EGCG/ECG binding. In summary, these galloylated epicatechins can be considered as potent protein-protein interaction (PPI) inhibitors that regulate CCL2-directed leukocyte recruitment for resolving inflammatory/immunomodulatory disorders.
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Base de datos:
MEDLINE
Asunto principal:
Catequina
/
Quimiocina CCL2
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Agric Food Chem
Año:
2023
Tipo del documento:
Article