ANTI-HIV ACTIVITY OF PHOSPHOROTHIOATE ANALOUGUES OF OLIGODEOXYNUCLEOTIDES

寡脱氧核苷酸硫代磷酸酯类似物的抗 HIV 活性

• 批准号: 3896338
• 负责人: R YARCHOAN
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3896338
• 关键词: AIDS; AIDS therapy; HIV infections; antiAIDS agent; antiviral agents; drug design /synthesis /production; human immunodeficiency virus 1; human immunodeficiency virus 2; human tissue; nucleotide analog; oligonucleotides; sulfur compounds; thioester; tissue /cell culture; virus cytopathogenic effect; virus infection mechanism; AIDS; AIDS therapy; HIV infections; antiAIDS agent; antiviral agents; drug design /synthesis /production; human immunodeficiency virus 1; human immunodeficiency virus 2; human tissue; nucleotide analog; oligonucleotides; sulfur compounds; thioester; tissue /cell culture; virus cytopathogenic effect; virus infection mechanism

Nuclease-resistant phosphorothioate analogues of oligodeoxynucleotides were synthesized by sulfurization of either internucleoside phosphite linkages, in a repetitive manner during chain extension, or internucleoside hydrogen phosphonate linkages, in a single step following chain assembly. These analogues were tested as antiviral agents against human immunodeficiency virus (HIV). In a cytopathic effect inhibition assay using HIV-uninfected susceptible T-cells (tetanus-toxoid specific normal T-cells) co-cultured with irradiated chronically HIV-infected cells, phosphorothioate oligomers inhibited the cytopathic effect and replication of several isolates of HIV-1 and HIV-2. Thus phosphorothioate analogues of oligodeoxynucleotides could inhibit cell-to-cell transmission of the virus as well as the infection by cell-free virus particles and also could inhibit variety of isolates of human retroviruses.

寡脱氧核苷酸的抗核酸酶的磷酸盐类似物为 两种核苷磷酸盐连接的硫化合成 在链延伸期间以重复的方式或核苷间氢以重复性的方式 膦酸酯连接，在链条组装后的一个步骤中。这些 类似物被视为针对人类免疫缺陷的抗病毒药物 病毒（HIV）。在使用HIV未感染的细胞病毒抑制测定中 易感的T细胞（破伤风特异性正常T细胞）共培养 与辐照的慢性艾滋病毒感染细胞，磷酸硫酸磷酸盐低聚物 抑制了几种分离株的细胞质效应和复制 HIV-1和HIV-2。因此 可以抑制病毒的细胞向细胞传播以及 无细胞病毒颗粒感染，也可能抑制多种多样 人类逆转录病毒的分离株。