North T W, Cronn R C, Remington K M, Tandberg R T
Division of Biological Sciences, University of Montana, Missoula 59812.
Antimicrob Agents Chemother. 1990 Aug;34(8):1505-7. doi: 10.1128/AAC.34.8.1505.
The sensitivities of reverse transcriptases (RTs) from feline immunodeficiency virus (FIV) and human immunodeficiency virus type 1 (HIV) were directly compared. The two enzymes had similar sensitivities to three analogs of dTTP, namely, 3'-azido-3'-deoxythymidine 5'-triphosphate, 2',3'-dideoxythymidine 5'-triphosphate, and 2',3'-dideoxy-2',3'-didehydrothymidine 5'-triphosphate. Each of these analogs demonstrated competitive inhibition of both enzymes. Ki values for inhibition of FIV RT by these three inhibitors were 3.3, 6.7, and 1.8 nM, respectively; Ki values for inhibition of the HIV enzyme were 6.5, 5.9, and 8.3 nM, respectively. Ratios of the Ki for the inhibitor to the Km for the substrate were also determined for each inhibitor, and no differences between the two enzymes greater than threefold were observed. Inhibition constants for 3'-amino-3'-deoxythymidine 5'-triphosphate and 3'-fluoro-3'-deoxythymidine 5'-triphosphate were determined for FIV RT, and these were similar to published values for HIV RT. The activities of three dideoxynucleoside 5'-triphosphates against FIV RT were determined; ddGTP was slightly more potent than ddTTP, whereas both were much more effective than ddCTP. The activity of a noncompetitive inhibitor, phosphonoformate, was also examined with the FIV enzyme; it was much more active with poly(rA)-oligo(dT) as the template-primer than with poly(rC)-oligo(dG) or poly(rI)-oligo(dC).
对猫免疫缺陷病毒（FIV）和1型人类免疫缺陷病毒（HIV）的逆转录酶（RT）敏感性进行了直接比较。这两种酶对三种dTTP类似物，即3'-叠氮-3'-脱氧胸苷5'-三磷酸、2'，3'-双脱氧胸苷5'-三磷酸和2'，3'-双脱氧-2'，3'-脱氢胸苷5'-三磷酸，具有相似的敏感性。这些类似物中的每一种都对两种酶表现出竞争性抑制作用。这三种抑制剂对FIV RT抑制的Ki值分别为3.3、6.7和1.8 nM；对HIV酶抑制的Ki值分别为6.5、5.9和8.3 nM。还测定了每种抑制剂的抑制剂Ki与底物Km的比值，未观察到两种酶之间的差异大于三倍。测定了3'-氨基-3'-脱氧胸苷5'-三磷酸和3'-氟-3'-脱氧胸苷5'-三磷酸对FIV RT的抑制常数，这些值与已发表的HIV RT值相似。测定了三种双脱氧核苷5'-三磷酸对FIV RT的活性；ddGTP比ddTTP稍强，而两者都比ddCTP有效得多。还用FIV酶检测了非竞争性抑制剂膦甲酸的活性；以聚（rA）-寡聚（dT）作为模板引物时，其活性比以聚（rC）-寡聚（dG）或聚（rI）-寡聚（dC）时高得多。
