PHOSPHORODITHIOATE DNA AS A POTENTIAL THERAPEUTIC DRUG
PHOSPHORODITHIOATE DNA AS A POTENTIAL THERAPEUTIC DRUG
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DOI：
10.1126/science.7681216
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发表时间：
1993-03-12
期刊：
影响因子：
56.9
通讯作者：
CARUTHERS, MH
中科院分区：
文献类型：
--
作者：
MARSHALL, WS;CARUTHERS, MH
本文总结了二硫代磷酸酯连接的脱氧寡核苷酸的合成方法，并详细分析了二硫代磷酸酯 DNA 寡聚体的独特特性之一，即其强烈抑制人类免疫缺陷病毒 1 型逆转录酶 (HIV-1 RT) 的能力。机理研究表明，这种类型的寡聚物通过与引物模板的活性位点紧密结合来干扰酶功能，从而导致低或亚纳摩尔抑制常数。尽管许多这些研究都使用了脱氧寡胞苷类似物，但合理设计的方法导致发现了一种非常活跃的二硫代磷酸脱氧寡核苷酸抑制剂。这种类型的抑制剂与 HIV-1 RT 的引物模板活性位点牢固结合，提供了另一种潜在的 HIV-1 治疗剂。
This article summarizes methods for the synthesis of phosphorodithioate-linked deoxyoligonucleotides and details an analysis of one of the distinctive properties of phosphorodithioate DNA oligomers, their ability to strongly inhibit human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT). Mechanistic studies indicate that oligomers of this type interfere with enzyme function by binding tightly to the active site for primer-template, which results in low or subnanomolar inhibitory constants. Although many of these studies have used deoxyoligocytidine analogs, a rationally designed approach has led to the discovery of a very active phosphorodithioate deoxyoligonucleotide inhibitor. This type of inhibitor, which binds strongly to the primer-template active site of HIV-1 RT, provides another type of potential therapeutic agent against HIV-1.