雄激素与其受体结合的定量手性

IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Piotr F. J. Lipiński, J. Dobrowolski, A. Baraniak
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引用次数: 0

摘要

手性是二元的是/否分子性质,但可以用连续的手性测度函数来描述。手性测量值可以理解为分子形状的敏感描述符。在这项研究中,我们评估了定量手性(测量)在雄激素与其受体结合中的作用。我们证明,在引入定量手性描述符作为附加变量后,将结合亲和力与药效氧原子的部分电荷相关联的简单定量构效关系方程得到了显著改进。在这样的模型中,电荷描述符解释了形成的氢键的强度。然而,手性测量间接包含了氢键网络的几何信息,以及与分子的不同局部或整体形状相连的范德瓦尔斯接触的细微差异,从而完成了这幅图景。本文研究的模型案例(11种简单且非常相似的类固醇)证明,在雄激素与其受体结合的过程中,全局和局部手性都很重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Quantitative chirality in the binding of androgens to their receptor
Chirality is a binary yes/no molecular property that nevertheless can be described by a continuous chirality measure function. Chirality measure values can be understood as sensitive descriptors of molecular shape. In this study, we evaluated the role of quantitative chirality (measures) in binding of androgens to their receptor. We demonstrate that a simple Quantitative Structure-Activity Relationship equation correlating the binding affinity with the partial charges of pharmacophoric oxygen atoms is significantly improved upon introducing quantitative chirality descriptors as additional variables. In such models, the charge descriptors account for the strength of the formed hydrogen bonds. However, the picture is completed by the chirality measures that indirectly contain information on the geometries of the hydrogen bond networks and subtle differences in the van der Waals contacts connected with different local or global shapes of the molecules. The model case studied here (11 simple and very similar steroids) proves that both global and local chirality is important in the androgen binding to their receptors.
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来源期刊
CiteScore
0.80
自引率
0.00%
发文量
74
审稿时长
6-12 weeks
期刊介绍: The international journal of the Polish Pharmaceutical Society is published in 6 issues a year. The journal offers Open Access publication of original research papers, short communications and reviews written in English, in all areas of pharmaceutical sciences. The following areas of pharmaceutical sciences are covered: Analysis, Biopharmacy, Drug Biochemistry, Drug Synthesis, Natural Drugs, Pharmaceutical Technology, Pharmacology and General. A bimonthly appearing in English since 1994, which continues “Acta Poloniae Pharmaceutica”, whose first issue appeared in December 1937. The war halted the activity of the journal’s creators. Issuance of “Acta Poloniae Pharmaceutica” was resumed in 1947. From 1947 the journal appeared irregularly, initially as a quarterly, then a bimonthly. In the years 1963 – 1973 alongside the Polish version appeared the English edition of the journal. Starting from 1974 only works in English are published in the journal. Since 1995 the journal has been appearing very regularly in two-month intervals (six books a year). The journal publishes original works from all fields of pharmacy, summaries of postdoctoral dissertations and laboratory notes.
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