2-卤代聚腺苷酸对鼠白血病病毒逆转录酶的抑制作用。
Inhibition of murine leukaemia virus reverse transcriptase by 2-halogenated polyadenylic acids.
作者信息
Fukui T, De Clercq E
出版信息
Biochem J. 1982 Jun 1;203(3):755-60. doi: 10.1042/bj2030755.
Several new analogues of polyadenylic acid [(A)n], i.e. poly(2-fluoroadenylic acid) [(fl2A)n], poly(2-chloroadenylic acid [(cl2A)n], poly(2-bromoadenylic acid) [(br2A)n] and poly(2-iodoadenylic acid) [(io2A)n] have been synthesized and evaluated for their effects on the RNA-directed DNA polymerase (reverse transcriptase) activity of Moloney murine leukaemia virus. All (A)n analogues were found to be potent inhibitors of reverse transcriptase, the order of (decreasing) potency being (fl2A)n greater than (io2A)n greater than (br2A)n greater than (cl2A)n. For all four (A)n analogues the inhibition of reverse transcriptase was competitive with respect to the template-primer. (A)n . oligo(dT). The K1 values were 0.02 microgram/ml for (fl2A)n, 0.1 microgram/ml for (io2A)n, 0.5 microgram/ml for (br2A)n and 8 microgram/ml for (cl2A)n. With a Ki of 0.02 microgram/ml (approx. 0.04 microM), (fl2A)n can be considered as one of the most, if not the most, potent polynucleotide inhibitor of reverse transcriptase that has been described so far.
已合成了几种聚腺苷酸[（A）n]的新类似物，即聚（2-氟腺苷酸）[（fl2A）n]、聚（2-氯腺苷酸）[（cl2A）n]、聚（2-溴腺苷酸）[（br2A）n]和聚（2-碘腺苷酸）[（io2A）n]，并评估了它们对莫洛尼鼠白血病病毒的RNA指导的DNA聚合酶（逆转录酶）活性的影响。发现所有（A）n类似物都是逆转录酶的有效抑制剂，（抑制效力递减）顺序为（fl2A）n大于（io2A）n大于（br2A）n大于（cl2A）n。对于所有四种（A）n类似物，逆转录酶的抑制作用相对于模板引物（A）n·寡聚（dT）是竞争性的。（fl2A）n的Ki值为0.02微克/毫升，（io2A）n为0.1微克/毫升，（br2A）n为0.5微克/毫升，（cl2A）n为8微克/毫升。（fl2A）n的Ki为0.02微克/毫升（约0.04微摩尔），可以认为是迄今为止描述的最有效的（如果不是最有效的）逆转录酶多核苷酸抑制剂之一。
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