Differential removal of thymidine nucleotide analogues from blocked DNA chains by human immunodeficiency virus reverse transcriptase in the presence of physiological concentrations of 2'-deoxynucleoside triphosphates.
Differential removal of thymidine nucleotide analogues from blocked DNA chains by human immunodeficiency virus reverse transcriptase in the presence of physiological concentrations of 2'-deoxynucleoside triphosphates.
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在生理浓度的 2-脱氧核苷三磷酸存在下，通过人免疫缺陷病毒逆转录酶从封闭的 DNA 链中差异性去除胸苷核苷酸类似物。
DOI：
10.1128/aac.44.12.3465-3472.2000
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发表时间：
2000
影响因子：
4.9
通讯作者：
Scott,WA
中科院分区：
文献类型：
--
作者：
Meyer,PR;Matsuura,SE;Schinazi,RF;So,AG;Scott,WA
通过人类免疫缺陷病毒 1 型 (HIV-1) 逆转录酶 (RT) 将链终止残基转移至核苷酸受体，可以从封闭的 DNA 链中去除 2',3'-二脱氢-3'-脱氧胸苷-5'-单磷酸 (d4TMP)。在 AZT 抗性 HIV-1 RT（含有 D67N/K70R/T215F/K219Q 突变）中，d4TMP 或 3'-叠氮基-3'-脱氧胸苷-5'-单磷酸 (AZTMP) 的 ATP 依赖性去除增加。 d4TMP 的去除受到下一个互补脱氧核苷三磷酸的强烈抑制（50% 抑制浓度 [IC50] ～0.5 μM），而 AZTMP 的去除对此抑制的敏感性要低得多（IC50 > 100 μM）。这可以解释在表型药物敏感性测定中，AZT 耐药的 HIV-1 对 d4T 缺乏交叉耐药性。
Removal of 2′,3′-didehydro-3′-deoxythymidine-5′-monophosphate (d4TMP) from a blocked DNA chain can occur through transfer of the chain-terminating residue to a nucleotide acceptor by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). ATP-dependent removal of either d4TMP or 3′-azido-3′-deoxythymidine-5′-monophosphate (AZTMP) is increased in AZT resistant HIV-1 RT (containing D67N/K70R/T215F/K219Q mutations). Removal of d4TMP is strongly inhibited by the next complementary deoxynucleoside triphosphate (50% inhibitory concentration [IC50] of ∼0.5 μM), whereas removal of AZTMP is much less sensitive to this inhibition (IC50of >100 μM). This could explain the lack of cross-resistance by AZT-resistant HIV-1 to d4T in phenotypic drug susceptibility assays.