{"title":"雄激素与其受体结合的定量手性","authors":"Piotr F. J. Lipiński, J. Dobrowolski, A. Baraniak","doi":"10.32383/appdr/161082","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":" ","pages":""},"PeriodicalIF":0.4000,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Quantitative chirality in the binding of androgens to their receptor\",\"authors\":\"Piotr F. J. Lipiński, J. Dobrowolski, A. Baraniak\",\"doi\":\"10.32383/appdr/161082\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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.\",\"PeriodicalId\":7147,\"journal\":{\"name\":\"Acta poloniae pharmaceutica\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.4000,\"publicationDate\":\"2023-03-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta poloniae pharmaceutica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.32383/appdr/161082\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta poloniae pharmaceutica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.32383/appdr/161082","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.