Loya S, Hizi A
Department of Cell Biology and Histology, Sackler School of Medicine, Tel-Aviv University, Israel.
FEBS Lett. 1990 Aug 20;269(1):131-4. doi: 10.1016/0014-5793(90)81137-d.
We have analyzed the effects of several natural compounds related to avarols and avarones on the catalytic functions of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). The most potent substances, designated as avarone A,B and E and avarol F, inhibited indiscriminately the enzymatic activities of HIV-1 RT, namely the RNA-dependent and DNA-dependent DNA polymerase as well as the ribonuclease H. The inhibition of the DNA polymerase activity was found to be non-competitive with respect to either the template-primer or the deoxynucleotidetriphosphate. These studies suggest that the hydroxyl group at the ortho position to the carbonyl group at the quinone ring is involved in blocking the RT activity. The identification of the active site of the inhibitors will hopefully lead to the rational design of new potent anti-HIV drugs.
我们分析了几种与avarols和avarones相关的天然化合物对人类免疫缺陷病毒1型（HIV-1）逆转录酶（RT）催化功能的影响。最有效的物质，命名为avarone A、B和E以及avarol F，无差别地抑制HIV-1 RT的酶活性，即依赖RNA和依赖DNA的DNA聚合酶以及核糖核酸酶H。发现DNA聚合酶活性的抑制相对于模板引物或脱氧核苷三磷酸而言是非竞争性的。这些研究表明，醌环上羰基邻位的羟基参与了对RT活性的阻断。抑制剂活性位点的确定有望导向新型高效抗HIV药物的合理设计。
