合成寡核糖核酸衍生物对人类免疫缺陷病毒（HIV-1）复制的抑制作用。
Inhibition of human immunodeficiency virus (HIV-1) replication by synthetic oligo-RNA derivatives.
作者信息
Shibahara S, Mukai S, Morisawa H, Nakashima H, Kobayashi S, Yamamoto N
机构信息
Central Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.
出版信息
Nucleic Acids Res. 1989 Jan 11;17(1):239-52. doi: 10.1093/nar/17.1.239.
Abstract
Several synthetic 2'-O-methyl-RNA oligomers and their derivatives have been evaluated for inhibitory effect against HIV-induced cytopathic effect and expression of the virus specific antigen in cultured MT-4 cells. In this study, oligo(2'-O-methyl)ribonucleoside phosphorothioates showed a potent inhibitory activity with size dependency (25-mer showed it at 1 microM), but by contrast both 2'-O-methylribo- and deoxy-oligomers with normal phosphate linkages failed to inhibit. However, it should be noted that the patched oligo(2'-O-methyl)ribonucleotide (20-mer), in which five linkages at 5'- and three linkages at 3'-ends of normal phosphates were replaced with thiophosphates, has recovered the substantial inhibitory effect. These results show that the size of oligomer and phosphorothioate linkages, probably resistant to exolytic nucleases, are essential for exhibiting antiviral activity.
摘要
已经评估了几种合成的2'-O-甲基-RNA寡聚物及其衍生物对HIV诱导的细胞病变效应和培养的MT-4细胞中病毒特异性抗原表达的抑制作用。在本研究中，寡聚（2'-O-甲基）核糖核苷硫代磷酸酯表现出强大的抑制活性，且具有大小依赖性（25聚体在1 microM时表现出该活性），但相比之下，具有正常磷酸酯键的2'-O-甲基核糖寡聚物和脱氧寡聚物均无抑制作用。然而，应该注意的是，在正常磷酸酯的5'-端有五个键和3'-端有三个键被硫代磷酸酯取代的拼接寡聚（2'-O-甲基）核糖核苷酸（20聚体）恢复了显著的抑制作用。这些结果表明，寡聚物的大小和硫代磷酸酯键（可能对核酸外切酶具有抗性）对于展现抗病毒活性至关重要。
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本文引用的文献
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Nucleic Acids Res. 1980 Nov 25;8(22):5473-89. doi: 10.1093/nar/8.22.5473.
2
Polymer support oligonucleotide synthesis XVIII: use of beta-cyanoethyl-N,N-dialkylamino-/N-morpholino phosphoramidite of deoxynucleosides for the synthesis of DNA fragments simplifying deprotection and isolation of the final product.聚合物载体寡核苷酸合成 XVIII：脱氧核苷的β-氰基乙基-N，N-二烷基氨基-/N-吗啉代亚磷酰胺用于 DNA 片段合成，简化最终产物的脱保护和分离
Nucleic Acids Res. 1984 Jun 11;12(11):4539-57. doi: 10.1093/nar/12.11.4539.
3
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4
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5
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6
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8
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