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2',5'-双-O-（叔丁基二甲基甲硅烷基）-3'-螺-5''-（4''-氨基-1'',2''-氧硫杂环戊烯-2'',2'-二氧化物）嘧啶（TSAO）核苷类似物：针对人类免疫缺陷病毒1型的高度选择性抑制剂，作用于病毒逆转录酶。

2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole-2'',2'-dioxide)pyrimidine (TSAO) nucleoside analogues: highlyselective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase.

作者信息

Balzarini J, Pérez-Pérez M J, San-Félix A, Schols D, Perno C F, Vandamme A M, Camarasa M J, De Clercq E

机构信息

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.

出版信息

Proc Natl Acad Sci U S A. 1992 May 15;89(10):4392-6. doi: 10.1073/pnas.89.10.4392.

DOI:10.1073/pnas.89.10.4392
PMID:1374900
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC49088/
Abstract

A series of pyrimidine nucleoside analogues containing [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino- 1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-ribofuranose as the pentose were found to inhibit human immunodeficiency virus type 1 [HIV-1(IIIB)] replication at a concentration of 0.06-0.8 microM but were not cytotoxic at a 1000- to 10,000-fold higher concentration. These nucleoside derivatives were also effective against various other HIV-1 strains, including those resistant to 3'-azido-3'-deoxythymidine, but not against HIV-2, simian immunodeficiency virus, Moloney murine sarcoma virus, or other RNA or DNA viruses. They proved to be highly specific inhibitors of the RNA-dependent DNA polymerase function of the HIV-1 reverse transcriptase, showing no marked inhibition of the HIV-1 reverse transcriptase-associated DNA-dependent DNA polymerase activity, HIV-2 reverse transcriptase, DNA polymerase alpha, herpes simplex virus 1 DNA polymerase, or Thermus aquaticus DNA polymerase.

摘要

一系列含有[2',5'-双-O-(叔丁基二甲基甲硅烷基)-3'-螺-5''-(4''-氨基-1'',2''-氧硫杂环戊烯-2'',2''-二氧化物)]-β-D-呋喃核糖作为戊糖的嘧啶核苷类似物被发现能在0.06 - 0.8微摩尔浓度下抑制1型人类免疫缺陷病毒[HIV-1(IIIB)]复制，但在高1000至10000倍的浓度下无细胞毒性。这些核苷衍生物对各种其他HIV-1毒株也有效，包括那些对3'-叠氮-3'-脱氧胸苷耐药的毒株，但对HIV-2、猴免疫缺陷病毒、莫洛尼鼠肉瘤病毒或其他RNA或DNA病毒无效。它们被证明是HIV-1逆转录酶的RNA依赖性DNA聚合酶功能的高度特异性抑制剂，对HIV-1逆转录酶相关的DNA依赖性DNA聚合酶活性、HIV-2逆转录酶、DNA聚合酶α、单纯疱疹病毒1 DNA聚合酶或嗜热栖热菌DNA聚合酶无明显抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8251/49088/e1546cb847ff/pnas01084-0185-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8251/49088/fd16e761ee4a/pnas01084-0184-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8251/49088/e1546cb847ff/pnas01084-0185-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8251/49088/fd16e761ee4a/pnas01084-0184-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8251/49088/e1546cb847ff/pnas01084-0185-a.jpg

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Proc Natl Acad Sci U S A. 1992 May 15;89(10):4392-6. doi: 10.1073/pnas.89.10.4392.
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