Phosphotriester formation by the haloethylnitrosoureas and repair of these lesions by E. coli BS21 extracts.

Phosphotriester formation by the haloethylnitrosoureas and repair of these lesions by E. coli BS21 extracts.
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卤乙基亚硝基脲形成磷酸三酯,大肠杆菌 BS21 提取物修复这些损伤。

DOI:
10.1093/nar/16.12.5661
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发表时间:
1988
影响因子:
14.9
通讯作者:
Ludlum,DB
Ludlum,DB
中科院分区:
生物学2区
文献类型:
--
作者:
Carter,CA;Kirk,MC;Ludlum,DB

文献摘要

被引文献

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研究了具有治疗活性的卤代乙基亚硝基脲(CNU)对DNA中磷酸盐的烷基化作用,方法是将N-氯乙基-N-亚硝基脲(CNU)与dTpdT反应,用HPLC分离产物,并与真实标记物共色谱鉴定。羟乙基和氯乙基磷酸三酯的dTpdT被确定; CNU和dTR之间的类似反应产生3-羟乙基和3-氯乙基dTR作为环烷基化的主要产物。用~(14)C标记的N-(2-氯乙基)-N′-环己基-N-亚硝基脲(~(14)CCNU)与聚dT反应,再退火形成聚dA,合成了一种用于修复研究的DNA样底物。colstrain BS 21选择性地将氯乙基从该底物中的一种氯乙基磷酸三酯异构体转移到细菌蛋白质;羟乙基磷酸三酯的化学不稳定性排除了关于该产物修复的明确结论。
The alkylation of phosphates in DNA by therapeutically active haloethylnitrosoureas was studied by reacting N-chloroethyl-N-nitrosourea (CNU) with dTpdT, separating the products by HPLC, and identifying them by cochromatography with authentic markers. Both hydroxyethyl and chloroethyl phosphotriesters of dTpdT were identified; a similar reaction between CNU and dTR yielded 3-hydroxyethyl and 3-chloroethyl dTR as the major products of ring alkylation. A DNA-like substrate for repair studies was synthesized by reacting14C-labelled N-(2-chloroethyl)-N′-cyclohexyl-N-nitrosourea (14C-CCNU) with poly dT and annealing the product to poly dA. An extract ofE. collstrain BS21 selectively transferred a chloroethyl group from one of the chloroethyl phosphotriester isomers in this substrate to the bacterial protein; chemical Instability of the hydroxyethyl phosphotriesters precluded definite conclusions about the repair of this product.