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首页> 美国卫生研究院文献>International Journal of Molecular Sciences >Differential Regulation of Bilastine Affinity for Human Histamine H
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Differential Regulation of Bilastine Affinity for Human Histamine H

机译：人组胺h的胆塑蝶亲和力的差异调节h

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摘要

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 roles of Lys179ECL2 and Lys1915.39 in regulating the electrostatic and hydrophobic binding of bilastine to H1 receptors by thermodynamic analyses. The binding enthalpy and entropy of bilastine were estimated from the van ’t Hoff equation using the dissociation constants. These constants were obtained from the displacement curves against the binding of [3H] mepyramine to membrane preparations of Chinese hamster ovary cells expressing wild-type human H1 receptors and their Lys179ECL2 or Lys1915.39 mutants to alanine at various temperatures. We found that the binding of bilastine to wild-type H1 receptors occurred by enthalpy-dependent binding forces and, more dominantly, entropy-dependent binding forces. The mutation of Lys179ECL2 and Lys1915.39 to alanine reduced the affinity of bilastine to H1 receptors by reducing enthalpy- and entropy-dependent binding forces, respectively. These results suggest that Lys179ECL2 and Lys1915.39 differentially contribute to the increased binding affinity to bilastine via electrostatic and hydrophobic binding forces.
机译：Bilastine，含有羧基的两性离子第二代抗组胺胺，对H1受体的选择性高于第一代抗组胺药。配体 - 受体对接模拟表明，第二代抗组胺瘤的羧基与人H1受体的Lys179Cl2和Lys1915.39的氨基之间的静电相互作用可能有助于这些抗组胺药对H1受体的亲和力。在该研究中，我们通过热力学分析评估了Lys179Cl2和Lys1915.39对百合碱对H1受体的静静压和疏水结合的作用。使用解离常数从VAN'T Hoff等式估计胆碱的结合焓和熵。这些常数是从置换曲线获得的，用于将[3H]甲嘧啶的结合与表达野生型人H1受体的膜制剂及其Lys179Cl2或Lys1915.39突变体在各种温度下对丙氨酸的膜制剂。我们发现，Bilastine与野生型H1受体的结合因焓依赖性结合力和更常见的熵依赖性结合力而发生。 Lys179Cl2和Lys1915.39的突变通过减少焓和熵依赖性结合力，将胆碱与H1受体的亲和力降低。这些结果表明Lys179Cl2和Lys1915.39差异地通过静电和疏水结合力对胆孢菌的增加的结合亲和力贡献。

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