Journal of molecular biochemistry最新文献

筛选
英文 中文
N2-Phenyl-9-(hydroxyalkyl)guanines and related compounds are substrates for Herpes simplex virus thymidine kinases. n2 -苯基-9-(羟基烷基)鸟嘌呤及其相关化合物是单纯疱疹病毒胸苷激酶的底物。
Journal of molecular biochemistry Pub Date : 2012-01-01
Andrea Lossani, Lida Savi, Andrzej Manikowski, Andrew Maioli, Joseph Gambino, Federico Focher, Silvio Spadari, George E Wright
{"title":"N<sup>2</sup>-Phenyl-9-(hydroxyalkyl)guanines and related compounds are substrates for Herpes simplex virus thymidine kinases.","authors":"Andrea Lossani,&nbsp;Lida Savi,&nbsp;Andrzej Manikowski,&nbsp;Andrew Maioli,&nbsp;Joseph Gambino,&nbsp;Federico Focher,&nbsp;Silvio Spadari,&nbsp;George E Wright","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Herpes simplex virus (HSV) types 1 and 2 thymidine kinases (TK) are responsible for phosphorylation of antiherpes acyclonucleosides such as acyclovir (ACV) and 9-(4-hydroxybutyl)guanine (HBG). Related compounds, the N<sup>2</sup>-phenyl-9-(hydroxyalkyl)guanines, are devoid of direct antiviral activity, but potently inhibit the viral TKs and block viral reactivation from latency <i>in vivo</i>. The similarity in structure between the acyclonucleosides and TK inhibitors raised the question of the relevance of phosphorylation of certain of the latter analogs in their mechanisms of action. Using recombinant TKs and HPLC analysis of reaction mixtures, we report that the lead TK inhibitor N<sup>2</sup>-phenyl-9 -(4-hydroxybutyl)guanine (HBPG) and its pentyl homolog (HPnPG) are excellent substrates for the enzymes, approaching the efficiency with which the natural substrate thymidine is phosphorylated, and significantly better than ACV or HBG. Other 9-hydroxyalkyl congeners are substrates for the enzymes, but with much poorer efficiency. HBPG triphosphate was a poor inhibitor of HSV DNA polymerase, the target of acyclonucleoside triphosphates, suggesting that phosphorylation of HBPG is not important in its mechanism of blocking viral reactivation <i>in vivo</i>. The fact that HBPG is an efficient substrate is consistent, however, with its binding mode based both on molecular modeling studies and x-ray structure of the HBPG:TK complex.</p>","PeriodicalId":73836,"journal":{"name":"Journal of molecular biochemistry","volume":"1 1","pages":"21-25"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984574/pdf/nihms556676.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32264606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信