Hizi A, Tal R, Shaharabany M, Currens M J, Boyd M R, Hughes S H, McMahon J B
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
Antimicrob Agents Chemother. 1993 May;37(5):1037-42. doi: 10.1128/AAC.37.5.1037.
We have studied the effects of four nonnucleoside inhibitors, including the novel natural product inhibitor calanolide A, on molecular chimeras containing complementary segments of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) reverse transcriptases (RTs). All four compounds specifically inhibited the DNA polymerase activity of HIV-1 RT but had no apparent effect on the RNase H activity of this enzyme or on the DNA polymerase or RNase H activity of HIV-2 RT. Three of these compounds showed the generally expected patterns of resistance and susceptibility with the various chimeric RTs. However, the inhibition patterns of the chimeric RTs by calanolide A provided evidence that there is a segment between residues 94 and 157 in HIV-1 RT that is critical for inhibition. However, the data also suggest that there may be a second segment located between amino acids 225 and 427 in HIV-1 RT that is also important for specifying susceptibility to the drug.
我们研究了四种非核苷抑制剂的作用，其中包括新型天然产物抑制剂卡拉诺利德A，该抑制剂作用于含有1型人类免疫缺陷病毒（HIV-1）和2型人类免疫缺陷病毒（HIV-2）逆转录酶（RT）互补片段的分子嵌合体。所有这四种化合物都特异性抑制HIV-1 RT的DNA聚合酶活性，但对该酶的核糖核酸酶H活性或HIV-2 RT的DNA聚合酶或核糖核酸酶H活性没有明显影响。其中三种化合物对各种嵌合RT表现出通常预期的耐药性和敏感性模式。然而，卡拉诺利德A对嵌合RT的抑制模式表明，HIV-1 RT中94至157位残基之间存在一个对抑制至关重要的片段。然而，数据还表明，HIV-1 RT中225至427位氨基酸之间可能存在第二个片段，该片段对于确定对该药物的敏感性也很重要。
