T Yamaguchi, M Kawarai, Y Takeshita, F Ishikawa, M Saneyoshi
{"title":"带有疏水基团的核苷酸类似物对人类端粒酶的抑制作用。","authors":"T Yamaguchi, M Kawarai, Y Takeshita, F Ishikawa, M Saneyoshi","doi":"10.1093/nass/44.1.175","DOIUrl":null,"url":null,"abstract":"<p><p>Telomerase, which synthesizes telomeric DNA in eukaryotic cells, is classified as a reverse transcriptase. To clarify the susceptibility of telomerase to nucleoside 5'-triphosphates bearing a hydrophobic group on the base moiety, we studied the inhibitory effects of 2',3'-dideoxy-5-styryluridine 5'-triphosphate analogues and 9-(beta-D-arabinofuranosyl)-2-(p-n-butylanilino)purine 5'-triphosphate analogues on telomerase activity using a quantitative 'stretch PCR' assay. 2',3'-Dideoxy-5-styryluridine 5'-triphosphate (StddUTP) showed more potent inhibition than 2',3'-dideoxythymidine 5'-triphosphate (ddTTP). On the other hand, 9-(beta-D-arabinofuranosyl)-2-(p-n-butylphenyl)guanine 5'-triphosphate (BuParaGTP) showed no inhibition, even though 9-(beta-D-arabinofuranosyl)guanine 5'-triphosphate (araGTP) is a potent inhibitor of telomerase. The influence on telomerase of hydrophobic substituents on the base moieties of nucleotides is described.</p>","PeriodicalId":19394,"journal":{"name":"Nucleic acids symposium series","volume":" 44","pages":"175-6"},"PeriodicalIF":0.0000,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/nass/44.1.175","citationCount":"3","resultStr":"{\"title\":\"Inhibition of human telomerase by nucleotide analogues bearing a hydrophobic group.\",\"authors\":\"T Yamaguchi, M Kawarai, Y Takeshita, F Ishikawa, M Saneyoshi\",\"doi\":\"10.1093/nass/44.1.175\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Telomerase, which synthesizes telomeric DNA in eukaryotic cells, is classified as a reverse transcriptase. To clarify the susceptibility of telomerase to nucleoside 5'-triphosphates bearing a hydrophobic group on the base moiety, we studied the inhibitory effects of 2',3'-dideoxy-5-styryluridine 5'-triphosphate analogues and 9-(beta-D-arabinofuranosyl)-2-(p-n-butylanilino)purine 5'-triphosphate analogues on telomerase activity using a quantitative 'stretch PCR' assay. 2',3'-Dideoxy-5-styryluridine 5'-triphosphate (StddUTP) showed more potent inhibition than 2',3'-dideoxythymidine 5'-triphosphate (ddTTP). On the other hand, 9-(beta-D-arabinofuranosyl)-2-(p-n-butylphenyl)guanine 5'-triphosphate (BuParaGTP) showed no inhibition, even though 9-(beta-D-arabinofuranosyl)guanine 5'-triphosphate (araGTP) is a potent inhibitor of telomerase. The influence on telomerase of hydrophobic substituents on the base moieties of nucleotides is described.</p>\",\"PeriodicalId\":19394,\"journal\":{\"name\":\"Nucleic acids symposium series\",\"volume\":\" 44\",\"pages\":\"175-6\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2000-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1093/nass/44.1.175\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nucleic acids symposium series\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/nass/44.1.175\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nucleic acids symposium series","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/nass/44.1.175","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3
摘要
端粒酶是一种逆转录酶,在真核细胞中合成端粒DNA。为了阐明端粒酶对碱基上带有疏水性基团的5'-三磷酸核苷的敏感性,我们使用定量“拉伸PCR”方法研究了2',3'-二脱氧-5-苯基尿苷5'-三磷酸类似物和9-(β -d -阿拉伯糖基)-2-(对-正丁基苯基)嘌呤5'-三磷酸类似物对端粒酶活性的抑制作用。2',3'-二脱氧-5-苯基尿嘧啶5'-三磷酸(StddUTP)比2',3'-二脱氧胸腺嘧啶5'-三磷酸(ddTTP)具有更强的抑制作用。另一方面,9-(β - d -阿拉伯糖基)-2-(对正丁基苯基)鸟嘌呤5'-三磷酸(BuParaGTP)没有抑制作用,尽管9-(β - d -阿拉伯糖基)鸟嘌呤5'-三磷酸(araGTP)是端粒酶的有效抑制剂。描述了核苷酸碱基上疏水取代基对端粒酶的影响。
Inhibition of human telomerase by nucleotide analogues bearing a hydrophobic group.
Telomerase, which synthesizes telomeric DNA in eukaryotic cells, is classified as a reverse transcriptase. To clarify the susceptibility of telomerase to nucleoside 5'-triphosphates bearing a hydrophobic group on the base moiety, we studied the inhibitory effects of 2',3'-dideoxy-5-styryluridine 5'-triphosphate analogues and 9-(beta-D-arabinofuranosyl)-2-(p-n-butylanilino)purine 5'-triphosphate analogues on telomerase activity using a quantitative 'stretch PCR' assay. 2',3'-Dideoxy-5-styryluridine 5'-triphosphate (StddUTP) showed more potent inhibition than 2',3'-dideoxythymidine 5'-triphosphate (ddTTP). On the other hand, 9-(beta-D-arabinofuranosyl)-2-(p-n-butylphenyl)guanine 5'-triphosphate (BuParaGTP) showed no inhibition, even though 9-(beta-D-arabinofuranosyl)guanine 5'-triphosphate (araGTP) is a potent inhibitor of telomerase. The influence on telomerase of hydrophobic substituents on the base moieties of nucleotides is described.