Conformations of complexes derived from the interactions of two stereoisomeric bay-region 5-methylchrysene diol epoxides with DNA.
Conformations of complexes derived from the interactions of two stereoisomeric bay-region 5-methylchrysene diol epoxides with DNA.
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源自两个立体异构湾区 5-甲基二醇环氧化物与 DNA 相互作用的复合物构象。
DOI：
10.1080/07391102.1986.10508476
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发表时间：
1986
影响因子：
4.4
通讯作者：
Harvey,RG
中科院分区：
文献类型：
--
作者：
Kim,MH;Roche,CJ;Geacintov,NE;Pope,M;Pataki,J;Harvey,RG
利用动力学流动二色性和荧光光谱技术研究了水溶液中5-甲基喹啉的两种同分异构体（反式-1，2-二羟基-反/-3，4-环氧-1，2，3，4-四氢-5-甲基喹啉（DE-I）和反式-7，8-二羟基-反-9，10-环氧-7，8，9，10-四氢-5-甲基喹啉（DE-II））与双链DNA的反应机理。与先前研究的苯并芘-7，8-二醇-9，10-氧化物异构体（BaPDE）一样，DE-I和DE-II都能迅速形成嵌入型复合物（在中性5 mM磷酸盐溶液中，缔合常数K分别为2700和1500 M− 1）。物理结合的二醇环氧化物分子以分钟的时间尺度反应，主要形成四醇; DE-I分子的比例（6±1%）大于DE-II分子（2-3%），与DNA反应形成共价产物。DE-II异构体的特征在于比DE-I更大的反应性，并且在两种情况下，在DNA存在下反应速率显著加快。共价加合物的线性二色性光谱表明，两种加合物的构象相似，菲基发色团的长轴相对于DNA碱基跃迁矩（260 nm处）的平均取向平均倾斜38-52°。共价结合的DE-I和DE-II分子的构象类似于在抗BaPDE的高度致瘤性（+）对映体的情况下观察到的构象。这些和其他多环芳香族二醇环氧化物的生物学性质的差异进行了讨论，在它们的反应性与DNA和形成的加合物的构象。
The reaction mechanisms of two isomeric bay-region diol epoxides of 5-methylchrysene (trans-1,2-dihydroxy-anti/-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (DE-I) andtrans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene (DE-II) with double-stranded DNA in aqueous solutions were studied utilizing kinetic flow dichroism and fluorescence techniques. As in the case of the previously studied benzo(a)pyrene-7,8-diol-9,10-oxide isomers (BaPDE), both DE-I and DE-II rapidly form intercalation-type complexes (association constants K = 2700 and 1500 M−1respectively in a neutral 5mM phosphate solution). The physically bound diol epoxide molecules react on time scales of minutes to form predominantly tetraols; a greater fraction (6±1%) of DE-I than of DE-II (2–3%) molecules react with the DNA to form covalent products. The DE-II isomer is characterized by a greater reactivity than DE-I, and the rates of reaction are markedly accelerated in the presence of DNA in both cases. The linear dichroism spectra of the covalent adducts reveal that the conformations of both types of adducts are similar, with the long axes of the phenanthrenyl chromophores tilted, on the average, at angles of 38-52° with respect to the average orientations of the transition moments (at 260 nm) of the DNA bases. The conformations of the covalently bound DE-I and DE-II molecules resemble those observed in the case of the highly tumorigenic (+) enantiomer ofanti-BaPDE. The differences in the biological properties of these and other polycyclic aromatic diol epoxides are discussed in terms of their reactivities with DNA and the conformations of the adducts formed.