寡脱氧核苷膦酸甲酯对获得性免疫缺陷综合征病毒的抑制作用。
Inhibition of acquired immunodeficiency syndrome virus by oligodeoxynucleoside methylphosphonates.
作者信息
Sarin P S, Agrawal S, Civeira M P, Goodchild J, Ikeuchi T, Zamecnik P C
机构信息
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, MD 20892.
出版信息
Proc Natl Acad Sci U S A. 1988 Oct;85(20):7448-51. doi: 10.1073/pnas.85.20.7448.
Abstract
Antisense oligodeoxynucleotides containing internucleoside methylphosphonate linkages were examined for their ability to inhibit human immunodeficiency virus (HIV)-induced syncytium formation and virus expression. HIV inhibitory activity was found to be dependent on both chain length and the number of phosphonate residues. Introduction of 18 phosphonate groups in an oligomer of chain length 20 significantly increased HIV inhibitory activity relative to the parent oligonucleotide, whereas 5 such groups showed little or no increase in the HIV inhibition capacity. Methylphosphonate-linked oligomers are more stable to nuclease degradation and hence could be potentially useful in the treatment of acquired immunodeficiency syndrome.
摘要
对含有核苷间甲基膦酸酯键的反义寡脱氧核苷酸抑制人类免疫缺陷病毒（HIV）诱导的合胞体形成及病毒表达的能力进行了研究。发现HIV抑制活性取决于链长和膦酸酯残基的数量。相对于亲本寡核苷酸，在链长为20的寡聚物中引入18个膦酸酯基团显著提高了HIV抑制活性，而5个这样的基团在HIV抑制能力上几乎没有增加或没有增加。甲基膦酸酯连接的寡聚物对核酸酶降解更稳定，因此在获得性免疫缺陷综合征的治疗中可能具有潜在用途。
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