D V Ianvarev, A N Korovina, N N Usanov, S N Kochetkov
{"title":"[Non-hydrolysable analogs of inorganic pyrophosphate as inhibitors of hepatitis C virus RNA-dependent RNA-polymerase].","authors":"D V Ianvarev, A N Korovina, N N Usanov, S N Kochetkov","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Inorganic pyrophosphate (PPi) is a product of the polymerization reaction catalyzed by DNA- and RNA-polymerases. We have synthesized a number of novel non-hydrolysable PPi analogues, some of them have demonstrated inhibition of polymerization reaction catalyzed by hepatitis C virus RNA-dependent RNA-polymerase (NS5B). A new pharmacophore has been developed based on non-hydrolysable methylene-diphosphonate backbone. Structure-activity relationship analysis of 12 bisphosphonates is presented and structural features crucial for the ability of molecule to inhibit NS5B polymerase activity are ascertained.</p>","PeriodicalId":9325,"journal":{"name":"Bioorganicheskaia khimiia","volume":"38 2","pages":"257-62"},"PeriodicalIF":0.0000,"publicationDate":"2012-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganicheskaia khimiia","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Inorganic pyrophosphate (PPi) is a product of the polymerization reaction catalyzed by DNA- and RNA-polymerases. We have synthesized a number of novel non-hydrolysable PPi analogues, some of them have demonstrated inhibition of polymerization reaction catalyzed by hepatitis C virus RNA-dependent RNA-polymerase (NS5B). A new pharmacophore has been developed based on non-hydrolysable methylene-diphosphonate backbone. Structure-activity relationship analysis of 12 bisphosphonates is presented and structural features crucial for the ability of molecule to inhibit NS5B polymerase activity are ascertained.