REACTION OF MONO- AND DI-FUNCTIONAL ALKYLATING AGENTS WITH NUCLEIC ACIDS
REACTION OF MONO- AND DI-FUNCTIONAL ALKYLATING AGENTS WITH NUCLEIC ACIDS
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DOI：
10.1042/bj0800496
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发表时间：
1961-01-01
影响因子：
4.1
通讯作者：
LAWLEY, PD
中科院分区：
文献类型：
--
作者：
BROOKES, P;LAWLEY, PD
在中性水溶液中，在37 ℃下，用各种烷基化试剂对RNA和DNA进行烷基化的速率和程度已经被测定。已显示烷基化发生在鸟嘌呤部分的N-7处，单官能试剂产生7-烷基鸟嘌呤，并且双官能试剂另外产生二（鸟嘌呤-7-基）衍生物。烷基化核糖核酸在中性水溶液中是稳定的，但烷基化脱氧核糖核酸分解时会损失烷基化鸟嘌呤产物。H3-标记的芥子气、S_（35）-标记的芥子气和2-羟乙基2-氯乙基[S_（35）]硫化物与小鼠埃里希腹水瘤细胞成分的结合程度以及H3-标记的芥子气与小鼠白血病细胞的结合程度已被确定。芥子气和2-羟乙基2-氯乙基硫化物与核酸在体内或体外反应的唯一区别是芥子气产生二-（β-鸟嘌呤-7-基）硫化物。芥子气作为小鼠腹水肿瘤生长抑制剂的有效性至少是2-羟乙基2-氯乙基硫化物的30倍。本文根据DNA结构的Crick-Watson模型讨论了单官能和双官能烷化剂与核酸的结合方式。本文还讨论了DNA烷基化反应与烷基化试剂生物学性质之间的可能关系。
The rates and extents of alkylation of RNA and DNA in neutral aqueous solution at 37[degree] by a variety of alkylating agents have been determined. Alkylation has been shown to occur at N-7 of guanine moieties, mono-functional agents yielding 7-alkylguanines, and difunctional agents yielding in addition di(guanin-7-yl) derivatives. Alkylated ribonucleic acid is stable in neutral aqueous solution but alkylated deoxyribonucleic acid decomposes with loss of the alkylated guanine products. The extent of binding has been determined of H3-labelled myleran, S35-labelled mustard gas and of 2-hydroxyethyl 2-chloroethyl [S35]sulphide to cellular constituents of the Ehrlich-ascites tumor and of H3-labelled myleran to leukemic cells in the mouse. The only difference found in vivo or in vitro for reaction of mustard gas and 2-hydroxyethyl 2-chloroethyl sulphide with nucleic acids is that mustard gas yields di-([beta]-guanin-7-yl) sulphide. Mustard gas is at least 30 times as effective as 2-hydroxyethyl 2-chloroethyl sulphide as an inhibitor of the growth of an ascites tumor in the mouse. The mode of combination of monofunqtional and of difunctional alkylating agents with nucleic acids is discussed in terms of the Crick-Watson model for the structure of DNA. The possible relationship between the alkylation of DNA and the bio-logicalproperties of the alkylating agents is discussed.