Gnabre J N, Brady J N, Clanton D J, Ito Y, Dittmer J, Bates R B, Huang R C
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11239-43. doi: 10.1073/pnas.92.24.11239.
A plant lignan, 3'-O-methyl nordihydroguaiaretic acid (3'-O-methyl NDGA, denoted Malachi 4:5-6 or Mal.4; molecular weigth 316), was isolated from Larrea tridentata and found to be able to inhibit human immunodeficiency virus (HIV) Tat-regulated transactivation in vivo, induce protection of lymphoblastoid CEM-SS cells from HIV (strain IIIB) killing, and suppress the replication of five HIV-1 strains (WM, MN, VS, JR-CSF, and IIIB) in mitogen-stimulated peripheral blood mononuclear cells, all in a dose-dependent manner. Mal.4 inhibits both basal transcription and Tat-regulated transactivation in vitro. The target of Mal.4 has been localized to nucleotides -87 to -40 of the HIV long terminal repeat. Mal.4 directly and specifically interferes with the binding of Sp1 to Sp1 sites in the HIV long terminal repeat. By inhibiting proviral expression, Mal.4 may be able to interrupt the life cycles of both wild-type and reverse transcriptase or protease mutant viruses in HIV-infected patients.
一种植物木脂素，3'-O-甲基去甲二氢愈创木酸（3'-O-甲基NDGA，记为玛拉基书4:5 - 6或Mal.4；分子量316），从三齿拉瑞阿（Larrea tridentata）中分离得到，发现其能够在体内抑制人类免疫缺陷病毒（HIV）Tat调节的反式激活，诱导淋巴母细胞CEM - SS细胞免受HIV（IIIB株）杀伤，并抑制五种HIV - 1毒株（WM、MN、VS、JR - CSF和IIIB）在有丝分裂原刺激的外周血单核细胞中的复制，所有这些均呈剂量依赖性。Mal.4在体外抑制基础转录和Tat调节的反式激活。Mal.4的作用靶点已定位到HIV长末端重复序列的核苷酸-87至-40。Mal.4直接且特异性地干扰Sp1与HIV长末端重复序列中Sp1位点的结合。通过抑制前病毒表达，Mal.4或许能够中断HIV感染患者体内野生型以及逆转录酶或蛋白酶突变病毒的生命周期。
