寡脱氧核苷磷酸酰胺酯和硫代磷酸酯作为人类免疫缺陷病毒的抑制剂
Oligodeoxynucleoside phosphoramidates and phosphorothioates as inhibitors of human immunodeficiency virus.
作者信息
Agrawal S, Goodchild J, Civeira M P, Thornton A H, Sarin P S, Zamecnik P C
机构信息
Worcester Foundation for Experimental Biology, Shrewsbury, MA 01545.
出版信息
Proc Natl Acad Sci U S A. 1988 Oct;85(19):7079-83. doi: 10.1073/pnas.85.19.7079.
Abstract
Modified oligodeoxynucleotides complementary to RNA of human immunodeficiency virus 1 (HIV-1) were tested for their ability to inhibit virally induced syncytium formation and expression of viral p24 protein. The modifications of oligomers include replacement of backbone phosphodiester groups with phosphorothioates and various phosphoramidates. All oligomers were found to be active. Oligomers with complete replacement of phosphodiesters with phosphoramidate or phosphorothioate groups were more active at the micromolar range than were unmodified oligomers of the same sequence. In addition, modified and unmodified homooligonucleotides also showed inhibition of HIV-1 replication. It is suggested that different classes of oligonucleotides may inhibit HIV replication by different mechanisms.
摘要
对与人类免疫缺陷病毒1型（HIV-1）RNA互补的修饰寡脱氧核苷酸进行了测试，以检测它们抑制病毒诱导的合胞体形成以及病毒p24蛋白表达的能力。寡聚物的修饰包括用硫代磷酸酯和各种氨基磷酸酯取代主链磷酸二酯基团。所有寡聚物均被发现具有活性。与相同序列的未修饰寡聚物相比，磷酸二酯被氨基磷酸酯或硫代磷酸酯基团完全取代的寡聚物在微摩尔范围内更具活性。此外，修饰和未修饰的同型寡核苷酸也显示出对HIV-1复制的抑制作用。有人提出，不同类别的寡核苷酸可能通过不同机制抑制HIV复制。
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