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(E)-5-(2-溴乙烯基)-2'-脱氧尿苷对单纯疱疹病毒1型特异性多肽合成的影响。

Effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on synthesis of herpes simplex virus type 1-specific polypeptides.

作者信息

Siegel S A, Otto M J, De Clercq E, Prusoff W H

出版信息

Antimicrob Agents Chemother. 1984 May;25(5):566-70. doi: 10.1128/AAC.25.5.566.

DOI:10.1128/AAC.25.5.566
PMID:6329089
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC185587/
Abstract

The antiherpesvirus agent (E)-5-(2-bromovinyl)-2'-deoxyuridine caused marked alterations in the synthesis and processing of several herpes simplex virus type 1 (HSV-1)-infected-cell polypeptides. Analogous to other thymidine analogs, there was a dose-dependent decrease in several beta and gamma polypeptides and an accumulation of HSV-1 thymidine kinase. In contrast to the action of other thymidine analogs, there were alterations in alpha polypeptides, including an increase in the synthesis and phosphorylation of infected-cell polypeptide 4b and a decrease in the synthesis of infected-cell polypeptide 27. The phosphorylation of several other HSV-1 phosphoproteins was mildly inhibited. (E)-5-(2-Bromovinyl)-2'-deoxyuridine inhibited the glycosylation of the major HSV-1 glycoproteins, and this activity appeared to be independent of the incorporation of the drug into the viral DNA. Thus, the alterations in HSV-1 polypeptide expression appear to be due to the presence of the drug in a low-molecular-weight form as well as its presence in the viral DNA. This suggests that this analog or a phosphorylated derivative might act as an inhibitor of an enzyme(s) responsible for posttranslational modification of polypeptides.

摘要

抗疱疹病毒药物(E)-5-(2-溴乙烯基)-2'-脱氧尿苷导致单纯疱疹病毒1型(HSV-1)感染细胞的几种多肽的合成和加工发生显著改变。与其他胸苷类似物相似,几种β和γ多肽呈剂量依赖性减少,HSV-1胸苷激酶积累。与其他胸苷类似物的作用相反,α多肽发生改变,包括感染细胞多肽4b的合成和磷酸化增加以及感染细胞多肽27的合成减少。其他几种HSV-1磷蛋白的磷酸化受到轻度抑制。(E)-5-(2-溴乙烯基)-2'-脱氧尿苷抑制HSV-1主要糖蛋白的糖基化,并且这种活性似乎与药物掺入病毒DNA无关。因此,HSV-1多肽表达的改变似乎是由于药物以低分子量形式存在以及其在病毒DNA中的存在。这表明该类似物或磷酸化衍生物可能作为负责多肽翻译后修饰的一种或多种酶的抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0693/185587/dc4950400068/aac00194-0043-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0693/185587/f763f63b83b1/aac00194-0041-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0693/185587/9cd4a7dc7887/aac00194-0042-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0693/185587/591897cd99ed/aac00194-0043-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0693/185587/dc4950400068/aac00194-0043-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0693/185587/f763f63b83b1/aac00194-0041-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0693/185587/9cd4a7dc7887/aac00194-0042-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0693/185587/591897cd99ed/aac00194-0043-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0693/185587/dc4950400068/aac00194-0043-b.jpg

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Problems associated with the use of (E)-5-(2-bromovinyl)-2'-deoxyuridine for typing herpes simplex virus.

本文引用的文献

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Antimicrob Agents Chemother. 1983 Jun;23(6):857-65. doi: 10.1128/AAC.23.6.857.
2
Methods for the complete analysis of 5-fluorouracil metabolites in cell extracts.细胞提取物中5-氟尿嘧啶代谢物的完整分析方法。
Anal Biochem. 1981 Oct;117(1):178-86. doi: 10.1016/0003-2697(81)90708-9.
3
Incorporation of 5-substituted analogs of deoxycytidine into DNA of herpes simplex virus-infected or - transformed cells without deamination to the thymidine analog.将脱氧胞苷的5-取代类似物掺入单纯疱疹病毒感染或转化细胞的DNA中,而不会脱氨基形成胸苷类似物。
与使用(E)-5-(2-溴乙烯基)-2'-脱氧尿苷进行单纯疱疹病毒分型相关的问题。
J Clin Microbiol. 1985 Mar;21(3):459-61. doi: 10.1128/jcm.21.3.459-461.1985.
Antimicrob Agents Chemother. 1983 Mar;23(3):465-76. doi: 10.1128/AAC.23.3.465.
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Possible molecular basis for antiviral activity of certain 5-substituted deoxyuridines.某些5-取代脱氧尿苷抗病毒活性的可能分子基础。
Antimicrob Agents Chemother. 1983 Mar;23(3):416-21. doi: 10.1128/AAC.23.3.416.
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Antimicrob Agents Chemother. 1983 Feb;23(2):332-4. doi: 10.1128/AAC.23.2.332.
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J Biol Chem. 1983 Jan 25;258(2):792-5.
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J Biol Chem. 1982 Jan 25;257(2):603-6.