Differential Regulation of Bilastine Affinity for Human Histamine H1 Receptors by Lys 179 and Lys 191 via Its Binding Enthalpy and Entropy

@article{Akimoto2021DifferentialRO,
  title={Differential Regulation of Bilastine Affinity for Human Histamine H1 Receptors by Lys 179 and Lys 191 via Its Binding Enthalpy and Entropy},
  author={Hayato Akimoto and Minoru Sugihara and Shigeru Hishinuma},
  journal={International Journal of Molecular Sciences},
  year={2021},
  volume={22}
}
Bilastine, a zwitterionic second-generation antihistamine containing a carboxyl group, has higher selectivity for H1 receptors than first-generation antihistamines. Ligand-receptor docking simulations have suggested that the electrostatic interaction between the carboxyl group of second-generation antihistamines and the amino group of Lys179ECL2 and Lys1915.39 of human H1 receptors might contribute to increased affinity of these antihistamines to H1 receptors. In this study, we evaluated the… Expand

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References

SHOWING 1-10 OF 36 REFERENCES
Roles of Lys191 and Lys179 in regulating thermodynamic binding forces of ligands to determine their binding affinity for human histamine H1 receptors.
TLDR
It is suggested that Lys1915.39 and Lys179ECL2 may not contribute to selectively increasing the binding affinity for carboxylated antihistamines via electrostatic interaction, but that they can negatively modulate thebinding affinity for non-carboxylation and carboxyated anti histamine non-selectively by affecting their electrostatic as well as hydrophobic binding forces. Expand
Differential Regulation of Thermodynamic Binding Forces of Levocetirizine and (S)-Cetirizine by Lys191 in Human Histamine H1 Receptors
TLDR
It is suggested that Lys 191 differentially regulates the binding enthalpy and entropy of these enantiomers, and that Lys191 negatively regulates theEnthalpy-dependent electrostatic binding forces of levocetirizine, contrary to the predictions derived from the ligand-receptor docking simulations. Expand
Differential thermodynamic driving force of first- and second-generation antihistamines to determine their binding affinity for human H1 receptors.
TLDR
It was found that entropy-dependent binding was more evident in second- than first-generation antihistamines, resulting in enthalpy-entropy compensation between the binding forces of first- and second-generationAntihistamines. Expand
Structure of the human histamine H1 receptor complex with doxepin
TLDR
Light is shed on the molecular basis of H1R antagonist specificity against H1r, demonstrating how minor differences in receptors lead to pronounced selectivity differences with small molecules. Expand
Preclinical Pharmacology of Bilastine, a New Selective Histamine H1 Receptor Antagonist
TLDR
These preclinical studies provide evidence that bilastine has H1-antihistamine activity, with high specificity for H 1-receptors, and poor or no affinity for other receptors. Expand
Contribution of Binding Enthalpy and Entropy to Affinity of Antagonist and Agonist Binding at Human and Guinea Pig Histamine H1-Receptor
TLDR
Thermodynamic analysis of ligand-binding may be a novel approach to dissect agonist- and antagonist-specific receptor conformations in GPCRs. Expand
The long duration of action of the second generation antihistamine bilastine coincides with its long residence time at the histamine H1 receptor
TLDR
The kinetics of bilastine binding to the human histamine H1 receptor is explored using [3H]mepyramine binding studies and its pharmacodynamics properties are compared to the reference compounds fexofenadine and diphenhydramine. Expand
Elucidation of Inverse Agonist Activity of Bilastine
TLDR
Preseasonal prophylactic administration with bilastine could down-regulate basal H1R gene expression in the nasal mucosa and ameliorate the nasal symptoms during the peak pollen period. Expand
Cherry-picked ligands at histamine receptor subtypes
TLDR
An overview on H1-R4Rs and developed ligands representing some key steps in development is provided here combined with a short description of structure-activity relationships for each class to support the rational choice for the optimal ligand selection based on affinity, selectivity and efficacy data in biochemical and pharmacological studies. Expand
Molecular properties and signalling pathways of the histamine H1 receptor
TLDR
Using molecular biological techniques, it is now possible to investigate ligand receptor interaction at the molecular level and it is expected that these new developments will provide much fundamental knowledge on the ligand interaction with the H1 receptor. Expand
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